Devices and methods for delivering therapeutic substances for the treatment of sinusitis and other disorders

ABSTRACT

Devices and methods for delivering drugs and other therapeutic or diagnostic substances to desired locations within the bodies of human or non-human animal subjects. An implantable delivery device comprising a reservoir is initially attached to a deliver catheter or delivery tool and is introduced into the body and positioned at a desired site. A therapeutic or diagnostic substance is then introduced into the reservoir and the delivery catheter or deliver tool is then removed, leaving the implantable delivery device implanted within the body. The substance is then delivered from the reservoir at a rate that causes the desire diagnostic or therapeutic effect. Also provided are substance eluting stents that elute substance from a selected surface of the stent (e.g., the outer surface) but not from another surface of the stent (e.g., the inner surface).

RELATED APPLICATIONS

This application is a continuation of copending U.S. patent applicationSer. No. 12/143,698 filed Jun. 20, 2008, which is a division of U.S.patent application Ser. No. 11/234,395 filed Sep. 23, 2005 and issued asU.S. Pat. No. 7,410,480, which is a continuation-in-part of U.S. patentapplication Ser. No. 10/829,917 filed on Apr. 21, 2004 and Ser. No.10/912,578 filed on Aug. 4, 2004 and issued as U.S. Pat. No. 7,361,168,the entire disclosure of each such application being expresslyincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to medical devices and methodsand more particularly to substance delivering implants and methods fortreating a broad range of disorders including but not limited tosinusitis and other ear, nose and throat disorders.

BACKGROUND

The paranasal sinuses are cavities formed within the bones of the face.The paranasal sinuses include frontal sinuses, ethmoid sinuses, sphenoidsinuses and maxillary sinuses. The paranasal sinuses are lined withmucous-producing epithelial tissue. Normally, mucous produced by thelinings of the paranasal sinuses slowly drains out of each sinus throughan opening known as an ostium, and into the nasopharnyx. Disorders thatinterfere with drainage of mucous (e.g., occlusion of the sinus ostia)can result in a reduced ability of the paranasal sinuses to functionnormally. This results in mucosal congestion within the paranasalsinuses. Such mucosal congestion of the sinuses can cause damage to theepithelium that lines the sinus with subsequent decreased oxygen tensionand microbial growth (e.g., a sinus infection).

The nasal turbinates are three (or sometimes four) bony processes thatextend inwardly from the lateral walls of the nasal cavity and arecovered with mucosal tissue. These turbinates serve to increase theinterior surface area of the nose and to impart warmth and moisture toair that is inhaled through the nose. The mucosal tissue that covers theturbinates is capable of becoming engorged with blood and swelling orbecoming substantially devoid of blood and shrinking, in response tochanges in physiologic or environmental conditions. The curved edge ofeach turbinate defines a passageway known as a meatus. For example, theinferior meatus is a passageway that passes beneath the inferiorturbinate. Ducts, known as the nasolacrimal ducts, drain tears from theeyes into the nose through openings located within the inferior meatus.The middle meatus is a passageway that extends inferior to the middleturbinate. The middle meatus contains the semilunar hiatus, withopenings or ostia leading into the maxillary, frontal, and anteriorethmoid sinuses. The superior meatus is located between the superior andmedial turbinates.

Nasal polyps are benign masses that grow from the lining of the nose orparanasal sinuses. Nasal polyps often result from chronic allergicrhinitis or other chronic inflammation of the nasal mucosa. Nasal polypsare also common in children who suffer from cystic fibrosis. In caseswhere nasal polyps develop to a point where they obstruct normaldrainage from the paranasal sinuses, they can cause sinusitis.

The term “sinusitis” refers generally to any inflammation or infectionof the paranasal sinuses. Sinusitis can be caused by bacteria, viruses,fungi (molds), allergies or combinations thereof.

Various drugs have been used to treat sinusitis, including systemicantibiotics. Intranasal corticosteroid sprays and intranasaldecongestant sprays and drops have also been used. However, the use ofintranasal sprays and drops by most patients does not result in the drugactually entering the affected intranasal sinuses. Rather, such spraysand drops typically contact only tissues located within the nasalcavity. The introduction of drugs directly into the sinuses has beenproposed by others, but has not become a widely used treatmenttechnique. For example, United States Patent Application Publication2004/0116958A1 (Gopferich et al.) describes a tubular sheath or “spacer”formed of biodegradable or non-biodegradable polymer that, prior toinsertion in the patient's body, is loaded with a controlled amount ofan active substance, such as a corticosteroid or anti-proliferativeagent. Surgery is performed to create a fenestration in a frontal sinusand the sheath is inserted into such fenestration. Thereafter, thesheath which has been preloaded with the active substance is insertedinto the surgically created fenestration where it a) deters closure ofthe surgically created fenestration, b) serves as a conduit tofacilitate drainage from the sinus and d) delivers the active substance.The sheath of United States Patent Application Publication2004/0116958A1 (Gopferich et al.) remains substantially in a singleconfiguration (i.e., it does not transition between a collapsedconfiguration and an expanded configuration) although it may be coatedwith a material that swells when in contact with mucous or body fluid.In some embodiments, the sheath is formed of multiple layers ofpolymeric material, one or more of which is/are loaded with the activesubstance and one or more of which is/are free of the active substance.In other embodiments, the sheath has a “hollow body” which forms areservoir system wherein the active substance is contained and amembrane which controls the release of the active substance from thereservoir. In some embodiments, the sheath may be anchored by causingthe end of the sheath that extends into the sinus to swell or otherwiseenlarge.

Also, Min, Yang-Gi, et al., Mucociliary Activity and Histopathology ofSinus Mucosa in Experimental Maxilary Sinusitis: A Comparison ofSystemic Administration of Antibiotic and Antibiotic Delivery byPolylactic Acid Polymer, Laryngoscope, 105:835-842 (August 1995)describes experiments wherein experimental sinusitis was induced inthree groups of rabbits by “pasting” the natural sinus ostia, forming anincision and small bore hole made in the anterior wall of the sinus,introducing pathogenic microbes through the bore hole and then closingthe incision. Five days after introduction of the pathogenic microbes,the natural sinus ostia were reopened and the rabbits were divided intothree (3) groups. Group 1 (control) received no treatment. Group 2received repeated intramuscular injections of ampicillin. In the animalsof Group 3, 1.5 cm×1.5 cm sheets of polylactic acid polymer (PLA) filmcontaining ampicillin (0.326 mg/sheet) were rolled up and insertedthrough the natural ostia into the infected sinuses. Thereafter,measurements of mucocilliary transport speed were made and the tissueslining the affected sinuses were examined histopathologically. Theauthors concluded that the therapeutic effect observed in the animalsthat had received intrasinus implants of PLA/Ampicillin film (Group 3)was significantly better that that observed in the untreated controlanimals (Group 1) or those that has received repeated intramusculardoses of ampicillin (Group 2).

U.S. Pat. No. 3,948,254 (Zaffaroni) describes implantable drug deliverydevices comprising a drug reservoir surrounded by a microporous wall.The reservoir may be formed of a solid drug carrier that is permeable topassage of the drug. The rate of passage of the drug through the wallmay be slower than the rate at which the drug passes through the soliddrug carrier that forms the reservoir. U.S. Pat. No. 3,948,254(Zaffaroni) describes a number of applications for the implantable drugdelivery devices including placement in a nasal passage. Specifically,U.S. Pat. No. 3,948,254 (Zaffaroni) claimed a nasal delivery device fordispensing a drug within a nasal passage at a controlled rate whereinthe nasal device is comprised of (a) a wall defining the devicedimensioned for insertion and placement within a nasal passage, with thewall formed of a nasal acceptable microporous material, (b) a reservoirsurrounded by the wall and comprised of a solid carrier permeable todrug and containing drug in an amount sufficient for the device to meterit at a continuous and controlled rate for a prolonged period of timefrom the device, (c) a liquid medium permeable to the passage of drug bydiffusion charged in the micropores, and (d) wherein the device releasesdrug when in a nasal environment by passage of drug from the carrier andthrough the liquid to the exterior of the device to produce a usefulresult. The entire disclosure of U.S. Pat. No. 3,948,254 (Zaffaroni) isexpressly incorporated herein by reference.

Other publications have also reported that introduction of drugsdirectly into the paranasal sinuses is effective in the treatment ofsinusitis. See, Tarasov, D. I., et al., Application of Drugs Based onPolymers in the Treatment of Acute and Chronic Maxillary Sinusitis,Vestn Otorinolaringol. Vol. 6, Pages 45-7 (1978). Also, R. Deutschmann,et al., A Contribution to the Topical Treatment of [Maxillary] SinusitisPreliminary Communication, Stomat. DDR 26 (1976), 585-592 describes theplacement of a resorbable drug delivery depot within the maxillary sinusfor the purposes of eluting drugs, specifically Chloramphenicol. In thisclinical series a water soluble gelatin was used as carrier and wasmixed with the drug prior to application and introduced as a mass intothe sinus. Since the substance had little mechanical integrity anddissolved in a relatively short timeframe, to achieve a therapeuticeffect, the author suggested that it must be instilled every 2 to 3days. An alternative to gelatin could be a sponge loaded with thetherapeutic substance as suggested in U.S. Pat. No. 6,398,758 (Jacobsen,et al.). In this patent directed at delivering a sustained releasedevice against the wall of a blood vessel, a hollow cylindrical spongeis loaded with drug and pressed against the wall. This allows the drugto contact the wall while sustaining blood flow within the center of thelumen. Further, a skin is provided to direct the drug into the walls ofthe blood vessel and prevent drug from flowing into the lumen. Whilesponges loaded with drug at the time of their application do permit somedegree of sustained release, the time required to load them alsocorrelates closely the time over which they will elute substance. Thus,if delivery is required for a longer period of time additionalmechanisms must be employed to regulate their release.

There are also several examples in the patent literature where varioussustained release mechanisms have generally been proposed using systemswith pre-incorporated drugs into matrices or polymers. These includeU.S. Pat. No. 3,948,254 (Zafferoni), US 2003/0185872A2 (Kochinke), WO92/15286 (Shikani), and U.S. Pat. No. 5,512,055 (Domb, et al.). Ingeneral, these references discuss various materials and structures thatmay be used to construct sustained drug delivery vehicles and provide agood overview of the state of sustained drug delivery art. While helpfulin laying out certain materials and schemes for creating sustainedrelease systems for drugs, each of these references, however, do notdescribe specific methods, means or structures which would permit themto be easily adapted for intended uses in the targeted in thisapplication.

Another common ear, nose and throat disorder is otitis media orinflammation of the middle ear. Most cases of otitis media areassociated with some degree of Eustachian tube disfunction. Because aircannot adequately pass through the Eustachian tube into the middle ear,negative pressure can be created within the middle ear. This negativepressure may essentially pull or draw fluid out of the lining of themiddle ear/mastoid, thereby resulting in an accumulation of fluid in themiddle ear behind the eardrum. In some cases, fluid that accumulateswithin the middle ear can become infected. Several types of otitis havebeen identified. Serous otitis typically results from a fairly suddenobstruction of the Eustachian tube and is characterized by thecollection of generally thin, clear fluid in the middle ear and mastoid.If this fluid does not clear within a few weeks, it is consideredchronic serous otitis. Secretory otitis typically occurs in smallchildren and is characterized by the collection of a thick fluid in themiddle ear and mastoid. This thick fluid contains muccoid material thathas been secreted by the mucous glands of the middle ear and alsocontains enzymes that can damage the small bones and other tissues ofthe middle ear. If left untreated, these enzymes can erode the bonesenough to cause permanent hearing loss. Acute otitis media ischaracterized by the accumulation of pus in the middle ear and typicallyoccurs in patients who have active respiratory infections which resultin an abrupt obstruction of the Eustachian tube at the same time asinfectious bacteria are present. Without antibiotic treatment, acuteotitis of bacterial origin can cause perforation of the eardrum, withdrainage of pus from the ear. Although the eardrum may heal after theinfection has resolved, permanent damage to the middle ear and/or theinner ear can sometimes result from infections of this severity. Chronicotitis media is typically caused by a form of chronic mastoiditis andresults in a chronic infection of the middle ear and mastoid cavity.Because the mastoid bone is involved, treatment with antibioticsadministered by traditional routes of administration (i.v., i.m., oral,etc.) sometimes does not remove the infection from the bone and surgicalremoval of the infected mastoid bone may be necessary. A commoncomplication associated with chronic otitis and mastoiditis ischolesteatoma. A cholesteatoma is a soft tissue sac that emanates fromthe eardrum and grows back into the middle ear or mastoid, therebycreating a mass of progressively increasing size which can destroy ordamage the bones of the middle ear, the inner ear, the facial nerveand/or portions of the brain. Thus, the various forms of otits can bevery serious if left untreated.

There remains a need in the art for the development of new devices andmethods for delivering drugs and other therapeutic or diagnosticsubstances into paranasal sinuses, Eustachian tubes, middle ear and/orother locations within the body for the treatment of sinusitis, otitisor other diseases and disorders.

SUMMARY OF THE INVENTION

In accordance with the present invention there is provided a substancedelivery device that generally comprises i) a removable portioncomprising an elongate shaft having a lumen and a distal end and ii) animplantable portion comprising a substance delivery reservoir having afirst configuration and a second configuration, said reservoir being incommunication with the lumen of the removable portion such that atherapeutic or diagnostic substance, or a component thereof, may beintroduced through the lumen and into the reservoir, said implantableportion being detachable from the removable portion such that theremovable portion may be removed from the subject's body leaving theimplantable portion within the subject's body. The reservoir maycomprise a balloon or other vessel that expands or otherwise changesconfiguration when filled with the diagnostic or therapeutic substance.The removable portion may include a lumen, advanceable needle, injectoror other substance introducing apparatus that is useable to introducethe desired substance, or a component thereof, into the reservoir afterthe reservoir has been introduced into the body. In addition todelivering the substance, all or part of the implantable portion of thedevice may function as a stent and/or scaffold and/or drain and/or vent.

Further in accordance with the present invention, there is provided amethod for using a substance delivery device of the above-summarizedcharacter, such method generally comprising the steps of; i) introducingthe substance delivery device into the subject's body while thereservoir is in a first configuration; ii) positioning the implantableportion at a desired location within the subject's body; iii) providinga therapeutic or diagnostic substance; iv) introducing the substance, ora component thereof, through the lumen and into the reservoir therebycausing the reservoir to assume the second configuration; v) detachingthe removable portion from the implantable portion; and vi) removing theremovable portion from the subject's body. In some embodiments of themethod the substance delivery device is implanted within the ear, nose,throat or paranasal sinus of the subject, but such methods also haveapplicability in many other areas of the body.

Still further in accordance with the invention, there is provided asubstance eluting implant (e.g., a stent) that generally comprises corethat contains the substance, a layer on one side of the core throughwhich the substance elutes and a layer on another side of the corethrough which substance does not elute. Thus, one surface (e.g., anouter tissue-contacting surface) of the implantable device may elute thesubstance while another surface (e.g., an inner or non-tissue contactingsurface) does not elute the substance.

Still further in accordance with the present invention, there isprovided a method for using a substance eluting implant of theabove-summarized character, such method generally comprising the step ofimplanting the implant within the body of a human or non-human animalsubject such that a substance eluting surface of the implant will elutethe substance and a non-substance eluting surface of the implant willnot elute any substantial amount of the substance.

Still further aspects and details of the present invention will beunderstood upon reading of the detailed description and examples setforth herebelow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a side view of an embodiment of a implantable sinussubstance delivery device disposed on a removable delivery catheter

FIG. 1A shows a perspective view of the sinus substance delivery deviceof FIG. 1.

FIGS. 1B and 1B′ show side views of the deployment mechanism of thesinus substance delivery device of FIG. 1 in the un-deployed anddeployed states respectively.

FIG. 1C shows a cross section through the plane 1C-1C of the deliverycatheter of FIG. 1.

FIG. 1D-1F show various steps of introducing and deploying the substancedelivery device of FIG. 1 into a paranasal sinus through the ostium ofthe paranasal sinus.

FIG. 2A shows a side view of an embodiment of a substance deliverydevice comprising a filling tube having a valve in the lumen of thefilling tube.

FIGS. 2B, 2C and 2D show cross sections of the device shown in FIG. 2Athrough the planes 2B-2B, 2C-2C and 2D-2D respectively.

FIGS. 2E and 2F show longitudinal cross sections of an embodiment of asubstance delivery device comprising a coaxial filling lumen and anelastomeric sleeve valve.

FIGS. 2G and 2H show cross sections through a portion of a substancedelivery device comprising an elastomeric sleeve valve located in aregion of an elongate shaft enclosed by a substance reservoir.

FIGS. 2I and 2J show a partial view of a region of a substance deliverydevice comprising a duck-bill valve.

FIGS. 2K and 2L show a partial view of a region of a substance deliverydevice comprising a dome valve.

FIGS. 2M and 2N show longitudinal sections through the filling mechanismof an embodiment of a substance delivery device comprising aself-sealing membrane.

FIGS. 2O and 2P show longitudinal sectional views of a region of anembodiment of a substance delivery device comprising a pluggingmechanism.

FIGS. 3A and 3B show a longitudinal section through a proximal region ofa substance delivery device deployed by a sliding tube.

FIGS. 4A through 4E show a coronal view of a human head showing thevarious steps of a method of delivering an implantable substancedelivery device to one of the paranasal sinuses of a patient.

FIGS. 4A through 4E show a coronal view of a human head showing thevarious steps of an embodiment of a method of delivering an implantablesubstance delivery device to a Eustachian tube or middle ear of apatient.

FIG. 4F shows a region of a substance delivery device comprising aninflatable balloon comprising two or more lobes.

FIG. 4G shows a cross section of the balloon shown in FIG. 4F throughthe plane 4G-4G.

FIG. 4H shows a perspective view of an embodiment of an inflatablesubstance reservoir comprising a spiral inflatable balloon.

FIG. 4I shows a perspective view of a region of a substance deliverydevice comprising an inflatable balloon having one or more radialprotrusions.

FIG. 4J shows a perspective view of a region of a substance deliverydevice comprising an inflatable balloon oriented transversely to theaxis of the substance delivery device.

FIG. 4K shows a substance delivery device comprising an inflatableballoon that acts as a substance reservoir.

FIG. 4L shows a section through a substance delivery device comprisingan inflatable substance delivery reservoir shaped to produce anatraumatic distal end.

FIG. 4M shows a cross section through a substance delivery devicecomprising two substance reservoirs that also act as anchors.

FIG. 4N shows a partial view of an embodiment of a substance deliverydevice comprising a substance reservoir made of foam.

FIG. 5A shows a sectional view of an embodiment of a drug deliverydevice comprising a pressure exerting mechanism.

FIG. 5A′ shows a sectional view of the substance delivery device shownin FIG. 5A showing the pressure exerting mechanism exerting a pressureon a substance reservoir.

FIG. 5B shows a cross sectional view of an embodiment of a substancedelivery device comprising a controlled substance release element in theform of a wick.

FIG. 5C shows the side view of an embodiment of an elongate porous tubethat may be used to control the rate of delivery of a substance to theanatomy from a substance delivery device.

FIG. 5D shows a cross sectional view of an embodiment of a substancedelivery device comprising the porous tube of FIG. 5C.

FIG. 5E shows a cross sectional view of an embodiment of a substancedelivery device comprising a porous shaft region for controlled deliveryof a substance to the anatomy.

FIG. 5F shows a cross section of the substance delivery device of FIG.5E through the plane 5F-5F.

FIG. 6A shows an embodiment of a substance delivery device comprising ananchoring or retention element comprising deployable arms.

FIG. 6A′ shows the substance delivery device of FIG. 6A deployed in asphenoid sinus.

FIG. 6B shows a perspective view of an embodiment of a substancedelivery device comprising a bent or angled shaft

FIG. 6B′ shows substance delivery device 610 of FIG. 6B deployed in asphenoid sinus.

FIG. 6C shows a perspective view of an embodiment of a substancedelivery device comprising a shaft comprising a curved or coiled region.

FIG. 6C′ shows the substance delivery device of FIG. 6C deployed in asphenoid sinus.

FIG. 6D shows a perspective view of an embodiment of a substancedelivery device comprising an elongate shaft comprising flexible,projections.

FIG. 6D′ shows the substance delivery device of FIG. 6D deployed in asphenoid sinus.

FIG. 6E shows a perspective view of an embodiment of a substancedelivery device comprising a substance reservoir having one or moreradial projections.

FIG. 6E′ shows substance delivery device 352 of FIG. 6E deployed in asphenoid sinus.

FIGS. 6F-6H show embodiment of substance delivery devices comprisingsuturing arrangement to suture the substance delivery devices toanatomical structures.

FIG. 7A shows a perspective view of an embodiment of a substancedelivery device comprising an elastic, super-elastic or shape-memorymaterial.

FIG. 7B shows a cross section through shaft 652 of substance deliverydevice 650 of FIG. 7A through the plane 7B-7B.

FIG. 7C shows the substance delivery device of FIG. 7A loaded on adelivery device.

FIG. 7D shows a cross section through the plane 7D-7D of FIG. 7B

FIG. 7E shows the substance delivery device of FIG. 7A loaded on thedelivery device of FIG. 7C being introduced through an elongateintroducing device.

FIG. 8A shows an embodiment of an elongate substance delivery devicecomprising an elongate filament being introduced in a sphenoid sinus.

FIG. 8B shows a cross sectional view through a region of the substancedelivery device of FIG. 8A through plane 8B-8B.

FIG. 9A shows a method of delivering a substance to the lateral wall ofa maxillary sinus by the substance delivery device of FIG. 5B.

FIG. 9B shows a method of delivering a substance to the medial wall of afrontal sinus by a device similar to the substance delivery device ofFIG. 4L.

FIGS. 10A through 10C show the various steps of a method of implanting asubstance delivering stent in an anatomical region.

FIG. 10D shows a cross section through a region 10D of an embodiment ofthe device of FIG. 10C.

FIGS. 11A through 11C show a sequence of steps to deliver a substancedelivery device through a sinus ostium that prevents post-surgicaladhesions and also allows the natural flow of mucous through the sinusostium.

DETAILED DESCRIPTION

The following detailed description and the accompanying drawings areintended to describe some, but not necessarily all, examples orembodiments of the invention only. This detailed description and theaccompanying drawings do not limit the scope of the invention in anyway.

The present invention provides devices that may be positioned withinnaturally occurring or man-made anatomical cavities such as a nostrils,nasal cavities, nasal meatus, ostia or interior of paranasal sinuses,etc.; or naturally occurring or man-made passageways such as Eustachiantubes, naso-lachrymal ducts, etc. to deliver a diagnostic or therapeuticsubstance to tissues located adjacent to or near the implanted device.Certain non-limiting examples of the present invention are shown inFIGS. 1-11C and described in detail herebelow. Although certain examplesshown in these drawings are targeted to the paranasal sinuses, regionsof the middle ear, Eustachian tubes, etc., the devices and methods ofthe present invention are useable in a wide range of applications invarious area of the body, including but not limited to natural or manmade orifices and passageways such as naso-lachrymal ducts, subcutaneouslocations, intravascular or intracardiac locations and locations withinthe gastrointestinal tract.

More specifically, one or more of the substance delivery devicesdisclosed herein may be positioned within natural or man-made openingsto the frontal, maxillary, sphenoid, anterior or posterior Ethmoidsinuses; other cells or cavities; anatomical regions such as nostrils,nasal cavities, nasal meatus, etc.; and other passageways such asEustachian tubes, naso-lachrymal ducts, etc. The step of placement ofthe substance delivery devices disclosed herein may be combined with astep of artificially creating an opening to an anatomical region. In oneembodiment, the substance delivery devices disclosed herein are placedthrough natural or dilated anterior or posterior ethmoid sinus ostia orartificially created openings to the ethmoid sinuses. The artificiallycreated openings may be created by punching a wall of the ethmoidsinuses. The sinus ostia or artificially created openings may beaccessed through one or more artificially created holes in the ethmoidbulla. Such artificially created holes in the ethmoid bulla may becreated by punching through the ethmoid bulla. In another embodiment,the substance delivery devices disclosed herein are placed throughartificially created openings to the maxillary sinuses.

The term substance as used herein is to be broadly construed to includeany feasible drugs, prodrugs, proteins, gene therapy preparations,cells, diagnostic agents, contrast or imaging agents, biologicals, etc.Such substances may be in bound or free form, liquid or solid, colloidor other suspension, solution or may be in the form of a gas or otherfluid or non-fluid. For example, in some applications where it isdesired to treat or prevent a microbial infection, the substancedelivered may comprise a pharmaceutically acceptable salt or dosage formof an antimicrobial agent (e.g., antibiotic, antiviral, antiparasitic,antifungal, etc.), a corticosteroid or other anti-inflammatory (e.g., anNSAID), a decongestant (e.g., vasoconstrictor), a mucous thinning agent(e.g., an expectorant or mucolytic), an agent that prevents of modifiesan allergic response (e.g., an antihistamine, cytokine inhibitor,leucotriene inhibitor, IgE inhibitor, immunomodulator), an anestheticagent with or without a vasoconstriction agents (e.g. Xylocaine with orwithout Epinephrine), an analgesic agent, an allergen or anothersubstance that causes secretion of mucous by tissues, hemostatic agentsto stop bleeding, anti-proliferative agents, cytotoxic agents e.g.alcohol, biological agents such as protein molecules, stem cells, genesor gene therapy preparations, viral vectors carrying proteins or nucleicacids such as DNA or mRNA coding for important therapeutic functions orsubstances, cauterizing agents e.g. silver nitrate, etc.

Some nonlimiting examples of antimicrobial agents that may be used inthis invention include acyclovir, amantadine, rimantadine, oseltamivir,zanamivir, aminoglycosides (e.g., amikacin, gentamicin and tobramycin),amoxicillin, amoxicillin/clavulanate, amphotericin B, ampicillin,ampicillin/sulbactam, atovaquone, azithromycin, cefazolin, cefepime,cefotaxime, cefotetan, cefpodoxime, ceftazidime, ceftizoxime,ceftriaxone, cefuroxime, cefuroxime axetil, cephalexin, chloramphenicol,clotrimazole, ciprofloxacin, clarithromycin, clindamycin, dapsone,dicloxacillin, doxycycline, erythromycin, fluconazole, foscarnet,ganciclovir, atifloxacin, imipenem/cilastatin, isoniazid, itraconazole,ketoconazole, metronidazole, nafcillin, nafcillin, nystatin, penicillinsincluding penicillin G, pentamidine, piperacillin/tazobactam, rifampin,quinupristin-dalfopristin, ticarcillin/clavulanate,trimethoprim/sulfamethoxazole, valacyclovir, vancomycin, mafenide,silver sulfadiazine, mupirocin, nystatin, triamcinolone/nystatin,clotrimazole/betamethasone, clotrimazole, ketoconazole, butoconazole,miconazole, tioconazole, detergent-like chemicals that disrupt ordisable microbes (e.g., nonoxynol-9, octoxynol-9, benzalkonium chloride,menfegol, and N-docasanol); chemicals that block microbial attachment totarget cells and/or inhibits entry of infectious pathogens (e.g.,sulphated and sulponated polymers such as PC-515 (carrageenan),Pro-2000, and Dextrin 2 Sulphate); antiretroviral agents (e.g., PMPAgel) that prevent retroviruses from replicating in the cells;genetically engineered or naturally occurring antibodies that combatpathogens such as anti-viral antibodies genetically engineered fromplants known as “plantibodies;” agents which change the condition of thetissue to make it hostile to the pathogen (such as substances whichalter mucosal pH (e.g., Buffer Gel and Acidform); non-pathogenic or“friendly” microbes that cause the production of hydrogen peroxide orother substances that kill or inhibit the growth of pathogenic microbes(e.g., lactobacillus); antimicrobial proteins or peptides such as thosedescribed in U.S. Pat. No. 6,716,813 (Lin et al,.) which is expresslyincorporated herein by reference or antimicrobial metals (e.g.,colloidal silver).

Additionally or alternatively, in some applications where it is desiredto treat or prevent inflammation the substances delivered in thisinvention may include various steroids or other anti-inflammatory agents(e.g., nonsteroidal anti-inflammatory agents or NSAIDs), analgesicagents or antipyretic agents. For example, corticosteroids that havepreviously administered by intranasal administration may be used, suchas beclomethasone (Vancenase® or Beconase®), flunisolide (Nasalide®),fluticasone proprionate (Flonase®), triamcinolone acetonide (Nasacort®),budesonide (Rhinocort Aqua®), loterednol etabonate (Locort) andmometasone (Nasonex®). Other salt forms of the aforementionedcorticosteroids may also be used. Also, other non-limiting examples ofsteroids that may be useable in the present invention include but arenot limited to aclometasone, desonide, hydrocortisone, betamethasone,clocortolone, desoximetasone, fluocinolone, flurandrenolide, mometasone,prednicarbate; amcinonide, desoximetasone, diflorasone, fluocinolone,fluocinonide, halcinonide, clobetasol, augmented betamethasone,diflorasone, halobetasol, prednisone, dexamethasone andmethylprednisolone. Other anti-inflammatory, analgesic or antipyreticagents that may be used include the nonselective COX inhibitors (e.g.,salicylic acid derivatives, aspirin, sodium salicylate, cholinemagnesium trisalicylate, salsalate, diflunisal, sulfasalazine andolsalazine; para-aminophenol derivatives such as acetaminophen; indoleand indene acetic acids such as indomethacin and sulindac; heteroarylacetic acids such as tolmetin, dicofenac and ketorolac; arylpropionicacids such as ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofenand oxaprozin; anthranilic acids (fenamates) such as mefenamic acid andmeloxicam; enolic acids such as the oxicams (piroxicam, meloxicam) andalkanones such as nabumetone) and Selective COX-2 Inhibitors (e.g.,diaryl-substituted furanones such as rofecoxib; diaryl-substitutedpyrazoles such as celecoxib; indole acetic acids such as etodolac andsulfonanilides such as nimesulide).

Additionally or alternatively, in some applications, such as those whereit is desired to treat or prevent an allergic or immune response and/orcellular proliferation, the substances delivered in this invention mayinclude a) various cytokine inhibitors such as humanized anti-cytokineantibodies, anti-cytokine receptor antibodies, recombinant (new cellresulting from genetic recombination) antagonists, or soluble receptors;b) various leucotriene modifiers such as zafirlukast, montelukast andzileuton; c) immunoglobulin E (IgE) inhibitors such as Omalizumab (ananti-IgE monoclonal antibody formerly called rhu Mab-E25) and secretoryleukocyte protease inhibitor).

Additionally or alternatively, in some applications, such as those whereit is desired to shrink mucosal tissue, cause decongestion or effecthemostasis, the substances delivered in this invention may includevarious vasoconstrictors for decongestant and or hemostatic purposesincluding but not limited to pseudoephedrine, xylometazoline,oxymetazoline, phenylephrine, epinephrine, etc.

Additionally or alternatively, in some applications, such as those whereit is desired to facilitate the flow of mucous, the substances deliveredin this invention may include various mucolytics or other agents thatmodify the viscosity or consistency of mucous or mucoid secretions,including but not limited to acetylcysteine (Mucomyst™, Mucosil™) andguaifenesin.

Additionally or alternatively, in some applications such as those whereit is desired to prevent or deter histamine release, the substancesdelivered in this invention may include various mast cell stabilizers ordrugs which prevent the release of histamine such as cromolyn (e.g.,Nasal Chrom®) and nedocromil.

Additionally or alternatively, in some applications such as those whereit is desired to prevent or inhibit the effect of histamine, thesubstances delivered in this invention may include variousantihistamines such as azelastine (e.g., Astylin®), diphenhydramine,loratidine, etc.

Additionally or alternatively, in some embodiments such as those whereit is desired to dissolve, degrade, cut, break or remodel bone orcartilage, the substances delivered in this invention may includesubstances that weaken or modify bone and/or cartilage to facilitateother procedures of this invention wherein bone or cartilage isremodeled, reshaped, broken or removed. One example of such an agentwould be a calcium chelator such as EDTA that could be injected ordelivered in a substance delivery implant next to a region of bone thatis to be remodeled or modified. Another example would be a preparationconsisting of or containing bone degrading cells such s osteoclasts.Other examples would include various enzymes of material that may softenor break down components of bone or cartilage such as collagenase (CGN),trypsin, trypsin/EDTA, hyaluronidase, and tosyllysylchloromethane(TLCM).

Additionally or alternatively, in some applications, the substancesdelivered in this invention may include other classes of substances thatare used to treat rhinitis, nasal polyps, nasal inflammation, and otherdisorders of the ear, nose and throat including but not limited toanti-cholinergic agents that tend to dry up nasal secretions such asipratropium (Atrovent Nasal®), as well as other agents not listed here.

Additionally or alternatively, in some applications such as those whereit is desired to draw fluid from polyps or edematous tissue, thesubstances delivered in this invention may include locally or topicallyacting diuretics such as furosemide and/or hyperosmolar agents such assodium chloride gel or other salt preparations that draw water fromtissue or substances that directly or indirectly change the osmolarcontent of the mucous to cause more water to exit the tissue to shrinkthe polyps directly at their site.

Additionally or alternatively, in some applications such as thosewherein it is desired to treat a tumor or cancerous lesion, thesubstances delivered in this invention may include antitumor agents(e.g., cancer chemotherapeutic agents, biological response modifiers,vascularization inhibitors, hormone receptor blockers, cryotherapeuticagents or other agents that destroy or inhibit neoplasia ortumorigenesis) such as; alkylating agents or other agents which directlykill cancer cells by attacking their DNA (e.g., cyclophosphamide,isophosphamide), nitrosoureas or other agents which kill cancer cells byinhibiting changes necessary for cellular DNA repair (e.g., carmustine(BCNU) and lomustine (CCNU)), antimetabolites and other agents thatblock cancer cell growth by interfering with certain cell functions,usually DNA synthesis (e.g., 6 mercaptopurine and 5-fluorouracil (5FU),antitumor antibiotics and other compounds that act by binding orintercalating DNA and preventing RNA synthesis (e.g., doxorubicin,daunorubicin, epirubicin, idarubicin, mitomycin-C and bleomycin) plant(vinca) alkaloids and other anti-tumor agents derived from plants (e.g.,vincristine and vinblastine), steroid hormones, hormone inhibitors,hormone receptor antagonists and other agents which affect the growth ofhormone-responsive cancers (e.g., tamoxifen, herceptin, aromataseinhibitors such as aminoglutethamide and formestane, triazole inhibitorssuch as letrozole and anastrazole, steroidal inhibitors such asexemestane), anti-angiogenic proteins, small molecules, gene therapiesand/or other agents that inhibit angiogenesis or vascularization oftumors (e.g., meth-1, meth-2, thalidomide), bevacizumab (Avastin),squalamine, endostatin, angiostatin, Angiozyme, AE-941 (Neovastat),CC-5013 (Revimid), medi-522 (Vitaxin), 2-methoxyestradiol (2ME2,Panzem), carboxyamidotriazole (CAI), combretastatin A4 prodrug (CA4P),SU6668, SU11248, BMS-275291, COL-3, EMD 121974, IMC-1C11, IM862,TNP-470, celecoxib (Celebrex), rofecoxib (Vioxx), interferon alpha,interleukin-12 (IL-12) or any of the compounds identified in ScienceVol. 289, Pages 1197-1201 (Aug. 17, 2000) which is expresslyincorporated herein by reference, biological response modifiers (e.g.,interferon, bacillus calmette-guerin (BCG), monoclonal antibodies,interluken 2, granulocyte colony stimulating factor (GCSF), etc.), PGDFreceptor antagonists, herceptin, asparaginase, busulphan, carboplatin,cisplatin, carmustine, cchlorambucil, cytarabine, dacarbazine,etoposide, flucarbazine, flurouracil, gemcitabine, hydroxyurea,ifosphamide, irinotecan, lomustine, melphalan, mercaptopurine,methotrexate, thioguanine, thiotepa, tomudex, topotecan, treosulfan,vinblastine, vincristine, mitoazitrone, oxaliplatin, procarbazine,streptocin, taxol, taxotere, analogs/congeners and derivatives of suchcompounds as well as other antitumor agents not listed here.

Additionally or alternatively, in some applications such as those whereit is desired to grow new cells or to modify existing cells, thesubstances delivered in this invention my include cells (mucosal cells,fibroblasts, stem cells or genetically engineered cells) as well asgenes and gene delivery vehicles like plasmids, adenoviral vectors ornaked DNA, mRNA, etc. injected with genes that code foranti-inflammatory substances, etc., and, as mentioned above, osteoclaststhat modify or soften bone when so desired.

Additionally or alternatively to being combined with a device and/or asubstance releasing modality, it may be ideal to position the device ina specific location upstream in the mucous flow path (i.e. frontal sinusor ethmoid cells). This could allow the deposition of fewer drugreleasing devices, and permit the “bathing” of all the downstreamtissues with the desired drug. This utilization of mucous as a carrierfor the drug may be ideal, especially since the concentrations for thedrug may be highest in regions where the mucous is retained; whereasnon-diseased regions with good mucous flow will be less affected by thedrug. This could be particularly useful in chronic sinusitis, or tumorswhere bringing the concentration of drug higher at those specific sitesmay have greater therapeutic benefit. In all such cases, local deliverywill permit these drugs to have much less systemic impact. Further, itmay be ideal to configure the composition of the drug or delivery systemsuch that it maintains a loose affinity to the mucous permitting it todistribute evenly in the flow. For example, one or more substanceeluting regions of a substance delivery device may be in physicalcontact with the mucous. Also, in some applications, rather than a drug,a solute such as a salt or other mucous soluble material may bepositioned at a location whereby mucous will contact the substance and aquantity of the substance will become dissolved in the mucous therebychanging some property (e.g., pH, osmolarity, etc) of the mucous. Insome cases, this technique may be used to render the mucous hyperosmolarso that the flowing mucous will draw water and/or other fluid frompolyps, edematous mucosal tissue, etc., thereby providing a drying ordesiccating therapeutic effect.

Additionally or alternatively to substances directed towards localdelivery to affect changes within the sinus cavity, the nasal cavitiesprovide unique access to the olfactory system and thus the brain. Any ofthe devices and methods described herein may also be used to deliversubstances to the brain or alter the functioning of the olfactorysystem. Such examples include, the delivery of energy or the depositionof devices and/or substances and/or substance delivering implant(s) toocclude or alter olfactory perception, to suppress appetite or otherwisetreat obesity, epilepsy (e.g., barbiturates such as phenobarbital ormephoobarbital; iminostilbenes such as carbamazepine and oxcarbazepine;succinimides such as ethylsuximide; valproic acid; benzodiazepines suchas clonazepam, clorazepate, diazepam and lorazepam, gabapentin,lamotrigine, acetazolamide, felbamate, levetiraceam, tiagabine,topiramate, zonisamide, etc.), personality or mental disorders (e.g.,antidepressants, antianxiety agents, antipsychotics, etc.), chronicpain, Parkinson's disease (e.g., dopamine receptor agonists such asbromocriptine, pergolide, ropinitrol and pramipexole; dopamineprecursors such as levodopa; COMT inhibitors such as tolcapone andentacapone; selegiline; muscarinic receptor antagonists such astrihexyphenidyl, benztropine and diphenhydramine) and Alzheimer'sdisease, Huntington's disease or other dementias, disorders of cognitionor chronic degenerative diseases (e.g. tacrine, donepezil, rivastigmine,galantamine, fluoxetine, carbamazepine, clozapine, clonazepam andproteins or genetic therapies that inhibit the formation of beta-amyloidplaques), etc.

The devices and methods disclosed herein may be used to deliver severalcombinations of two or more substances disclosed herein to a suitabletarget anatomical region. In one particular embodiment, the devices andmethods disclosed herein are used to deliver a combination of ananti-inflammatory agent (e.g. a steroid or an NSAID) and a mucolyticagent.

The inner surface of some anatomical regions such as paranasal sinusesis lined by mucous. This mucous is continuously generated within theparanasal sinuses. Simultaneously, this mucous continuously flows out ofparanasal sinuses through an ostium of the paranasal sinuses. Thus,substance delivered to a paranasal sinus tends to be lost from theparanasal sinus along with the mucous flow. This reduces the net amountof the substance remaining in the paranasal sinus. Hence, there exists aneed to replenish the substance delivered to the paranasal sinus tomaintain an effective amount of the substance in the paranasal sinus. Inorder to address this need, one or more of the substance deliverydevices disclosed herein may comprise one or more substance reservoirsto allow an effective amount of a substance to be delivered to targetanatomical regions over an effective period of time.

Turning now to FIGS. 1-11C, it is to be understood that such figuresshow specific examples of the devices and methods of the presentinvention. Any elements, attributes, components, accessories or featuresof one embodiment or example shown in these figures may be eliminatedfrom that embodiment or example, or may be included in any otherembodiment or example, unless to do so would render the resultantembodiment or example unusable for its intended purpose.

FIG. 1 shows a side view of an embodiment of a device of the presentinvention comprising an implantable sinus substance delivery device 100(e.g., an implantable portion) and a removable delivery catheter 102(e.g, a removable portion). The implantable substance delivery device100 is disposed on and is delivered by the removable delivery catheter102. The implantable portion or substance delivery device 100 of thisexample comprises a tube or elongate shaft 104 and a substance reservoir106 from which a desired substance is eluted or otherwise delivered.Elongate shaft 104 may be made of suitable biocompatible materialsincluding, but not limited to Pebax, PEEK, Nylon, polyethylene, etc.This tube or elongate shaft may function and a stent and/or drain and/orvent when implanted. In this regard, the elongate shaft 104 mayincorporate one or more lumens that are designed to allow drainage ofsecretions or other fluid substances and/or ventilation of air intodesired anatomical regions (e.g., paranasal sinuses, the middle ear,etc. Additionally or alternatively, the elongate shaft 104 of theimplantable portion 102 may incorporate a substance introducing lumenthat may be used to fill a reservoir 106 with fluid substances. Asdescribed in more detail below, the implantable drug delivery device 100may also incorporate apparatus for preventing backflow of substance outof the reservoir 106 after the removable delivery catheter 102 has beenremoved. For example, the implantable substance delivery device 100 mayhave a substance introducing lumen through which a substance, or acomponent of the substance, may be introduced into the reservoir 106 anda check valve may be posititioned within that substance introducinglumen and/or within the reservoir to prevent backflow out of thatsubstance introducing lumen. In this regard, the substance introducinglumen may have a collapsible or elastomeric region that is biased to aclosed or collapsed configuration so as to thereby act as a valve. Thiscollapsible or elastomeric region will then expand when a user isfilling reservoir 106 with a fluid substance under pressure, thusallowing the fluid substance to flow into the reservoir 106. Thesubstance introducing lumen may be detachably connected to reservoir106. In some embodiments, the reservoir 106 may be inflatable orexpandable. In such inflatable or expandable embodiments, the reservoir106 may be inflated or expanded in situ, after it has been implanted orotherwise positioned in a desired anatomical location. Thus the profileof substance delivery device 100 is reduced during the step ofintroducing reservoir 106 in the desired anatomical location. The lumenof elongate shaft 104 may be fitted with a one way valve to preventunwanted drainage of a substance used to fill reservoir 106. In theembodiment shown in FIG. 1, reservoir 106 comprises a balloon that maybe made from suitable biocompatible materials such as polyurethane,polyethylene, Nylon, etc. The balloon may comprise one or more pores oropenings to allow delivery of the substance in reservoir 106 to thesurrounding anatomy. Those pores or openings may be sized to allow thesubstance to be delivered from the reservoir 106 at a desired rate.

In some embodiments, a navigational marker 108 such as a radiopaquemarker band may be present on elongate shaft 104 in the region enclosedby drug reservoir 106 or elsewhere on the device. The substance deliverydevice 100 is introduced into and advanced to a desired implantationsite or target anatomy by the removable delivery catheter 102. Thedelivery catheter 102 provides support to substance delivery device 100while substance delivery device 100 is introduced into and is deliveredto the target anatomy. Delivery catheter 102 is also used to fillsubstance delivery device 100 with a suitable substance to be deliveredto the anatomy. Delivery catheter 102 comprises an elongate shaft 110that can be made of suitable biocompatible materials including, but notlimited to metals e.g. stainless steel, titanium, Nickel-titanium alloy(e.g., Nitinol), etc.; polymers e.g. Pebax, PEEK, Nylon, polyethylene,etc. In one embodiment, the proximal end of elongate shaft 110 comprisesa hub 112 such as a female luer hub. Hub 112 is in fluid communicationwith a lumen of elongate shaft 110. The lumen of elongate shaft 110 isin fluid communication with the lumen of elongate shaft 104 used to fillreservoir 106. The distal end of elongate shaft 110 is detachablyconnected to the proximal end of elongate shaft 104. Delivery catheter102 may further comprise a deployment mechanism for deploying substancedelivery device 100 in a desired location in the anatomy. In theembodiment shown in FIG. 1, the deployment mechanism comprises a pushingtube 114 that can be made of suitable biocompatible materials including,but not limited to Pebax, PEEK, Nylon, polyethylene, etc. Pushing tube114 encloses and slides on elongate tube 110. To deploy substancedelivery device 100 in the anatomy, a user pushes pushing tube 114 inthe distal direction. The distal end of pushing tube 114 then pushes aproximal region of elongate shaft 104 that is detachably attached toelongate shaft 110. This causes substance delivery device 100 to detachfrom delivery catheter 102 thereby implant substance delivery device 100in the anatomy. After implanting substance delivery device 100 in theanatomy, delivery catheter 102 is removed from the anatomy.

FIG. 1A shows a perspective view of sinus substance delivery device 100showing elongate shaft 104 and reservoir 106 and navigational marker 108located on elongate shaft 104.

FIGS. 1B and 1B′ show side views of the deployment mechanism of thesinus substance delivery device of FIG. 1 in the un-deployed anddeployed states respectively. In FIG. 1B, the proximal end of elongateshaft 104 of substance delivery device 100 is detachably attached to thedistal end of elongate shaft 110 of delivery catheter 102. In FIG. 1B′,a user pushes pushing tube 114 in the distal direction over elongateshaft 110. The distal end of pushing tube 114 pushes elongate shaft 104.This causes the proximal end of elongate shaft 104 to detach from thedistal end of elongate shaft 110. This in turn causes substance deliverydevice 100 to detach from delivery catheter 102, thereby deployingsubstance delivery device 100 in the anatomy.

FIG. 1C shows a cross section through the plane 1C-1C of removabledelivery catheter 102 of FIG. 1. FIG. 10 shows pushing tube 114 over theouter surface of elongate shaft 110. Elongate shaft 110 enclosesguidewire GW.

FIG. 1D-1F show various steps of introducing and deploying implantablesubstance delivery device 100 of FIG. 1 into a paranasal sinus throughthe ostium of the paranasal sinus by a removable removable deliverycatheter 102.

Substance delivery device 100 may be advanced into the anatomy by asuitable introducing device. In one embodiment, substance deliverydevice 100 is advanced into the anatomy by a suitable guidewire GW asshown in FIGS. 1D-1F. In this embodiment, substance delivery device 100may comprise one or more arrangements to allow a user to introducesubstance delivery device 100 over the guidewire. For example, elongateshaft 104 may comprise an end-to-end guidewire lumen, a rapid exchangeguidewire lumen, etc. In another embodiment, substance delivery device100 is advanced into the anatomy through a suitable guide catheter.

Substance delivery device 100 may be inserted into an anatomical regionsuch as a paranasal sinus of a patient through natural ostia as shown inFIGS. 1D-1F or artificially created openings of the paranasal sinus.Substance delivery device 100 may be inserted into the paranasal sinusbefore or after sinus procedures such as FESS or Balloon Sinuplasty™.Substance delivery device 100 may be used to prevent or reduce postprocedural scarring or adhesions and/or to provide ventilation ordrainage of the paranasal sinus. Substance delivery device 100 maycomprise one or more anchors or other retaining mechanisms to maintainthe position of substance delivery device 100 inside the paranasal sinusfor a desired treatment duration. In one embodiment, inflated reservoir106 acts as an anchor. Substance delivery device 100 may be designed toallow its removal from the anatomy without the use of ionizing radiationsuch as X-rays.

The length of the implantable substance delivery device 100 may rangefrom about 20 mm to about 80 mm. The combined length of the implantablesubstance delivery device 100 and the removable delivery catheter 102may range from about 15 cm to about 135 cm.

In two preferred embodiments, the length of substance delivery device100 is around 5 cm. Hub 112 is a luer lock. This enables a user to filla suitable substance into reservoir 106 using a standard syringe. Thelength of the delivery system from the proximal end of the female luerhub to the distal end of elongate shaft 110 is around 25 cm. Elongateshaft 104 comprises a monorail guidewire lumen. The inner diameter ofthe monorail guidewire lumen is 0.037″. This enables a user to introducesubstance delivery device 100 into an anatomical region over a suitable0.035″ guidewire. Substance delivery device 100 and the suitable 0.035″guidewire may be delivered through a guide catheter of inner diameter0.100″. The filling lumen of elongate shaft 104 comprises a one waymicro-valve. The micro-valve is located 4 cm proximal to the distal tipof elongate shaft 104. In an alternate embodiment, the micro-valve islocated 1 cm from the distal tip of elongate shaft 104. Reservoir 106comprises an elastomeric balloon of an inflated diameter ranging from7-10 mm. The elastomeric balloon may be made from suitable biocompatiblematerials such as polyurethane, polyethylene, Nylon, etc. The length ofthe elastomeric balloon is about 10 mm. The inflated elastomeric balloonacts as an anchor to retain the position of substance delivery device100 in the anatomy. A user may remove substance delivery device 100 fromthe anatomy by gently pulling substance delivery device 100. Theelastomeric balloon is designed to touch at least one mucosal region inthe anatomy after substance delivery device 100 is introduced in theanatomy. The substance stored in reservoir 106 may be delivered to thesurrounding anatomy through one or more pores located on the elastomericballoon or on a distal region of elongate shaft 104. In the firstpreferred embodiment, the elastomeric balloon comprises two microporesof diameter 80 microns. The two micropores are located on diagonallyopposite regions on the proximal tapered region of the elastomericballoon. This first embodiment was filled with 0.15 ml of distilledwater at 37 degrees Celsius. The rate of delivery of the distilled waterwas measured in a shaker bath. This embodiment of substance deliverydevice 100 delivered 0.006-0.017 ml of distilled water in 15 hours. Inthe second preferred embodiment, a single micropore is located onelongate shaft 104. The micropore is located 10 mm from distal tip ofelongate shaft 104. The micropore has a pore size of 60 microns. Theelastomeric balloon was then inflated with 0.2 ml of a Kenalog solutionand the rate of release of the Kenalog solution was measured in a shakerbath at a temperature of 37 degrees Celsius. This embodiment ofsubstance delivery device 100 delivered 0.12-0.18 ml of the Kenalogsolution in 24 hours.

The various substance delivery devices disclosed herein may comprise oneor more substance reservoirs that are introduced in the anatomy in afirst configuration. Thereafter, the reservoirs are filled with asuitable substance. This causes the reservoirs to assume a secondconfiguration. Such a reservoir design having two or more configurationsis especially useful to reduce the profile of the substance deliverydevices while introducing the substance delivery devices in the anatomy.Such a reservoir design is also useful when the reservoir acts as ananchor. For example, substance delivery device 100 comprises aninflatable reservoir 106. Reservoir 106 is introduced in the anatomy inthe un-inflated first configuration to reduce the profile of reservoir106. Thereafter, reservoir 106 is filled with a suitable substance tocause reservoir 106 to assume a inflated second configuration.

The various substance delivery devices disclosed herein may comprise oneor more rate limiting barriers to regulate the delivery of the substancestored in the substance delivery device to the surrounding anatomy. Forexample, in the two preferred embodiments described in the previousparagraph, the rate limiting barrier comprises micropores or apertureslocated on an elastomeric balloon or on a region of the elongate shaft.The rate limiting barrier may be designed to regulate the delivery ofthe substance to the surrounding anatomy based on one or more chemicalor physical properties of the substance. In one embodiment, the ratelimiting barrier is designed to regulate the delivery of the substanceto the surrounding anatomy based on the viscosity of the substance. Inanother embodiment, the rate limiting barrier is designed to regulatethe delivery of the substance to the surrounding anatomy based on themolecular weight of the substance. In another embodiment, the ratelimiting barrier is designed to regulate the delivery of the substanceto the surrounding anatomy based on the electric charge of the moleculesof the substance. In another embodiment, the rate limiting barrier isdesigned to regulate the delivery of the substance to the surroundinganatomy based on the osmolarity or osmolality of the substance. Inanother embodiment, the rate limiting barrier is designed to regulatethe delivery of the substance to the surrounding anatomy based on thehydrophobic or hydrophilic nature of the molecules of the substance. Inanother embodiment, the rate limiting barrier is designed to regulatethe delivery of the substance to the surrounding anatomy based on thepresence of a certain chemical group or atom in the molecules of thesubstance. In another embodiment, the rate limiting barrier is asemipermeable barrier. The semipermeable barrier may be designed tocontain pores of a known size or a distribution of sizes to regulate thedelivery of the substance to the surrounding anatomy.

The reservoirs of the substance delivery devices disclosed herein may befilled with a suitable substance through a substance introducing lumenlocated in a substance filling tube. Such a filling tube may be providedwith one or more closure apparatus or mechanisms to prevent unwantedleakage of the suitable substance through the lumen of the substancefilling tube. Examples of such closure apparatus or mechanisms include,but are not limited to valves such as check valves, clipping mechanisms,plugging mechanisms, etc. The valves may be located on the region of asubstance delivery device enclosed by a substance reservoir. FIG. 2Ashows a side view of an embodiment of a substance delivery devicecomprising a filling tube having a valve in the lumen of the fillingtube. Substance delivery device 118 comprises a substance reservoir 106.Substance reservoir 106 comprises a means for delivering a storedsubstance to the surrounding anatomy over a period of time. In theexample shown in FIG. 2A, substance reservoir 106 is an inflatableballoon. The length of the inflatable balloon may range from 10-20 mm.The inflated diameter of the inflatable balloon ranges preferably from7-10 mm. The inflatable balloon is preferably made from suitableelastomeric materials including, but not limited to low densitypolyethylene, low durometer Pebax, polyurethane, etc. The inflatableballoon may also act as an anchor to secure the position of substancereservoir 106 in the anatomy. In one method embodiment, substancereservoir 106 is inserted into a paranasal sinus through the ostium ofthe paranasal sinus. Thereafter, the inflatable balloon is inflated witha suitable substance such that the size of the inflatable balloon isgreater than the size of the ostium of the paranasal sinus. Theinflatable balloon then acts as an anchor to secure the position ofsubstance reservoir 106 in the paranasal sinus. Substance reservoir 106can be filled with a suitable substance by an elongate shaft 104 thatacts as a filling tube. Elongate shaft 104 comprises a lumen. A valve120 is present in elongate shaft 104. In the example shown in FIG. 2A,valve 120 is a duck-bill valve. Other examples of valves include, butare not limited to flutter valves, slit valves, relief valves comprisingsprings, poppet valves, valves comprising one or more leaflets, etc.Valve 120 allows a user to fill substance reservoir 106. Valve 120 alsoprevents leakage of the substance from the proximal end of elongateshaft 104. In the example shown in FIG. 2A, valve 120 is located about3-5 cm from the proximal end of substance reservoir 106. Alternatively,valve 120 may be located in the region of elongate shaft 104 enclosed bysubstance reservoir 106. In one embodiment, the outer diameter of theregion of substance delivery device 118 enclosing valve 120 ranges from2-3 mm. The proximal region of elongate shaft 104 may comprise asuitable hub such as a luer lock. Alternatively, the proximal region ofelongate shaft 104 may be attached to the distal region of a second tube122. The proximal region of second tube 122 may comprise a suitable hubsuch as a luer lock 112. Second tube 122 is made preferably frommaterials such as low density polyethylene, Pebax, polyurethane, etc.The attachment between the proximal region of elongate shaft 104 and thedistal region of a second tube 122 may be non-detachable or detachable.In one embodiment the outer diameter of second tube 122 is around 0.05inches and the inner diameter is around 0.03 inches. Substance deliverydevice 118 may comprise one or more mechanisms to allow substancedelivery device 118 to be introduced in the anatomy along introducingdevices. For example, substance delivery device 118 may be introducedover suitable guidewires, through suitable guide catheters, etc. In theexample shown in FIG. 2A, substance delivery device 118 comprises arapid exchange lumen located in a parallel tube 124 that is parallel toelongate shaft 104. In one embodiment, the outer diameter of paralleltube 124 is 0.048 inches and the inner diameter of parallel tube 124 is0.038 inches. The distal region of the inflatable balloon is fixed to aregion of parallel tube 124 to form a distal balloon joint. In oneembodiment, the length of the distal balloon joint ranges from 2-3 mm.The proximal region of the inflatable balloon is fixed to a region ofparallel tube 124 and elongate shaft 104 to form a proximal balloonjoint. In one embodiment, the length of the proximal balloon jointranges from 2-4 mm. The length from the proximal end of the proximalballoon joint till the proximal end of parallel tube 124 may range from2-3 cm. The length from the distal end of the distal balloon joint tillthe distal end of parallel tube 124 may range from 1-2 mm. Substancedelivery device 118 may comprise a marker 126 to allow the position ofsubstance delivery device 118 to be tracked in the anatomy. In theexample shown in FIG. 2A, marker 126 is a radiopaque marker. In oneembodiment, the length of substance delivery device 118 measured fromthe distal end of hub 112 till the distal end of parallel tube 124 isaround 30 cm.

FIGS. 2B, 2C and 2D show cross sections of the device shown in FIG. 2Athrough the planes 2B-2B, 2C-2C and 2D-2D respectively. FIG. 2B shows across section of parallel tube 124. FIG. 2C shows a cross section ofelongate shaft 104 and parallel tube 124. FIG. 2D shows a cross sectionof second tube 122.

Various novel elastomeric sleeve valves may be used to design thevarious embodiments of the substance delivery devices disclosed herein.Such elastomeric sleeve valves comprise a sleeve or tubular piece of anelastomeric substance that is located near an opening of a reservoirfilling lumen. For example, FIGS. 2E and 2F show longitudinal crosssections of an embodiment of a substance delivery device comprising acoaxial filling lumen and an elastomeric sleeve valve. Substancedelivery device 127 of FIG. 2E comprises a substance reservoir 106.Substance reservoir 202 comprises a means for delivering a storedsubstance to the surrounding anatomy over a period of time. In theexample shown in FIG. 2E, substance reservoir 106 is an inflatableballoon. The length of the inflatable balloon may range from 10-20 mm.The inflated diameter of the inflatable balloon ranges preferably from7-10 mm. The inflatable balloon is preferably made from suitableelastomeric materials including, but not limited to low densitypolyethylene, low durometer Pebax, polyurethane, etc. Substance deliverydevice 126 further comprises a coaxial tube comprising an outer tube 128and an inner tube 130. Inner tube 130 comprises a first lumen 132. Theregion between outer tube 128 and inner tube 130 encloses a coaxialsecond lumen 134. In one embodiment, second lumen 134 is a substanceintroducing lumen used to fill substance reservoir 106. Substancedelivery device 126 further comprises a second tube 136. The regionbetween the inner surface of second tube 136 and the outer surface ofthe coaxial tube encloses a third lumen 138. In the example shown inFIG. 2E, the proximal end of the inflatable balloon is attached to adistal region of second tube. The distal end of the inflatable balloonis attached to the distal region of inner tube 130. Substance deliverydevice 126 further comprises a one way elastomeric sleeve valve 140. Inthe example shown in FIG. 2E, valve 140 comprises an elongate tubeenclosing a lumen. Valve 140 can be made of suitable biocompatiblematerials including, but not limited to C-flex™, Kraton™, polyurethane,LDPE, silicone, EVA, other thermoplastic elastomers, etc. The one end ofvalve 140 is attached to a region of outer tube 128 by a fluid tightseal. The other end of valve is unattached. The unattached region ofvalve 140 compresses on the outer surface of inner tube 130 to sealsecond lumen 134 from third lumen 138. In FIG. 2E, a user introduces asubstance in second lumen 134 under pressure. The pressure from secondlumen 134 causes the unattached region of valve 140 to expand as shown.This causes the substance to travel from second lumen 134 to third lumen138 and fills substance reservoir 106. In FIG. 2F, the introduction ofthe substance into second lumen 134 is stopped. This releases thepressure on valve 140 from second lumen 134. Thus the unattached regionof valve 140 compresses on the outer surface of inner tube 130. Thisseals second lumen 134 from third lumen 138 thereby preventing theempting of substance reservoir 106 through second lumen 134. First lumen132 may be used to introduce substance delivery device 126 into theanatomy over an introducing device such as a guidewire.

The shafts of the substance delivery devices disclosed herein maycomprise one or more valves present in the region enclosed by asubstance reservoir. For example, FIGS. 2G and 2H show cross sectionsthrough a portion of a substance delivery device comprising anelastomeric sleeve valve located in a region of an elongate shaftenclosed by a substance reservoir. FIG. 2G shows a cross sectional viewof a drug delivery device 144 comprising an elongate shaft 104. Elongateshaft 104 may be made of suitable biocompatible materials including, butnot limited to Pebax, PEEK, Nylon, polyethylene, etc. Elongate shaft 104encloses a substance introducing lumen 146. A distal region of lumen 146is blocked by a plug 148. A substance reservoir 106 is located on adistal region of elongate shaft 104. In the example shown in FIG. 2G,substance delivery reservoir comprises an inflatable balloon. Theinflatable balloon is preferably made from suitable elastomericmaterials including, but not limited to low density polyethylene, lowdurometer Pebax, polyurethane, etc. Lumen 146 is in fluid communicationwith substance reservoir 106 through one or more first openings or pores150. Lumen 146 may thus be used to fill substance reservoir 106 with asuitable substance. An elastomeric sleeve valve 152 is located nearfirst openings or pores 150. Valve 152 allows the substance to flow fromlumen 146 to substance reservoir 106. Also, valve 152 prevents orsubstantially reduces the flow of the substance from substance reservoir106 to lumen 146. In the example shown in FIG. 2G, valve 152 comprisesan elongate tube enclosing a lumen. Valve 152 can be made of suitablebiocompatible materials including, including, but not limited toC-flex™, Kraton™, polyurethane, LDPE, silicone, EVA, other thermoplasticelastomers, etc. One end of valve 152 is attached to a region ofelongate tube 104 by a fluid tight seal. The other end of valve 152 isunattached. The unattached region of valve 152 compresses on the outersurface of elongate tube 104 to seal substance reservoir 106 from lumen146. In FIG. 2G, a user introduces a substance in lumen 146 underpressure. The pressure from lumen 146 causes the unattached region ofvalve 152 to expand as shown. This causes the substance to flow fromlumen 146 to substance reservoir 106. In FIG. 2H, the introduction ofthe substance into lumen 146 is stopped. This releases the pressure onvalve 152 from lumen 146. Thus the unattached region of valve 152compresses on the outer surface of elongate tube 104. This seals lumen146 from substance reservoir 106 thereby preventing or substantiallyreducing the flow of the substance from substance reservoir 106 to lumen146. The substance stored in substance reservoir 106 is controllablyreleased into the surrounding anatomy through a substance deliverymechanism. In the example shown in FIGS. 2G and 2H, the substancedelivery mechanism comprises one or more second openings or pores 154that create a fluid communication between substance reservoir 106 andlumen 146. The distal end of lumen 146 opens into the surroundinganatomy such that the substance flows from substance reservoir 106 tothe surrounding anatomy.

Valve 140 and valve 152 are made from elastomeric materials including,but not limited to C-flex™, Kraton™, polyurethane, LDPE, silicone, etc.The preferred thickness of the wall of the material of valve 140 andvalve 152 ranges from 0.001 inches to 0.008 inches. The preferredlongitudinal length of valve 140 and valve 152 ranges from 4-10 mm.Valve 140 and valve 152 may attached to an outer surface of elongateshafts by a variety of attachment mechanisms. In one embodiment of anattachment mechanism, valve 140 and valve 152 are attached by suitablebiocompatible adhesives. For example, an adhesive such as Loctite® 4011may be used with or without primers such as Loctite® 7701. In anotherembodiment of an attachment mechanism, valve 140 and valve 152 areattached to the elongate shafts by the mechanical compressive force ofthe elastomeric material of the valves. In another embodiment of anattachment mechanism, a cylindrical piece of heat-shrink tubing isclamped around a region of valve 140 and valve 152. In anotherembodiment of an attachment mechanism, valve 140 and valve 152 are laserwelded or thermally welded to the elongate shafts.

The substance delivery devices disclosed herein may comprise varioustypes of one-way valves. Such one-way valves enable a user to fill asubstance reservoir with a suitable substance, but prevent the backflowof the substance after the substance reservoir is filled. For example,FIGS. 2I and 2J show a partial view of a region of a substance deliverydevice comprising a duck-bill valve. FIG. 2I shows a region of asubstance delivery device 158 comprising a hollow shaft 160. Hollowshaft 160 encloses a reservoir filling lumen. A duck-bill valve 162 isprovided in the substance introducing lumen of hollow shaft 160.Duck-bill valve 162 comprises a hollow body 164 enclosing a lumen. Thedistal region of duck-bill valve 162 comprises two or more leaflets 166.In one embodiment, duck-bill valve 162 is attached to the inner surfaceof hollow shaft 160 by a suitable adhesive. In the embodiment shown inFIG. 2I, the inner surface of hollow shaft 160 comprises a notch 168. Anouter region of hollow body 164 of duck-bill valve 162 is locked innotch 168 as shown to attach duck-bill valve 162 to hollow shaft 160.Duck-bill valve 162 allows the flow of a fluid in the distal directionalong hollow shaft 160. This enables a user to fill a substancereservoir located distal to duck-bill valve 162. Duck-bill valve 162prevents the flow of fluid in the proximal direction along hollow shaft160. This prevents unwanted drainage of the fluid substance from thesubstance reservoir through hollows shaft 160. FIG. 2J shows the step offilling the substance reservoir of substance delivery device 158 byinserting a fluid substance through the proximal region of hollow shaft160. The pressure of the fluid substance spreads apart two or moreleaflets 166 to open duck-bill valve 162. This allows the flow of thefluid substance in the distal direction along hollow shaft 160.Duck-bill valve 162 may be made from suitable biocompatible materialsincluding, but not limited to elastomeric materials such as silicone,fluorosilicone, etc. In one embodiment, duck-bill valve 162 is made froma single piece of a suitable material.

FIGS. 2K and 2L show a partial view of a region of a substance deliverydevice comprising a dome valve. FIG. 2K shows a region of a substancedelivery device 170 comprising a hollow shaft 172. Hollow shaft 172encloses a reservoir filling lumen. A dome valve 174 is provided in thelumen of hollow shaft 172. Dome valve 174 comprises a hollow body 176enclosing a lumen. The distal region of dome valve 174 comprises a dome178. One or more slits 180 are located in the distal most region of dome178. To introduce a fluid substance in the lumen of hollow shaft 172distal to dome valve 174, a user inserts an injecting device throughslits 180 as shown in FIG. 2L. In the embodiment shown in FIGS. 2K and2L, the injecting device comprises a hollow shaft 182 enclosing a lumen.Hollow shaft 182 comprises an atraumatic distal end. Hollow shaft 182further comprises an opening or pore 184 that creates a fluidcommunication between the lumen of hollow shaft 182 and the exterior ofhollow shaft 182. Slits 180 allow the passage of the injecting devicethrough them while maintaining a substantial fluid seal around theinjecting device. The user can then introduce the fluid substancethrough the lumen of the injecting device to fill a substance reservoirlocated distal to dome valve 174. After the injecting device iswithdrawn, dome valve 174 prevents the flow of fluid in the proximaldirection along hollow shaft 172. This prevents unwanted drainage of thefluid substance from the substance reservoir through hollows shaft 172.In one embodiment, dome valve 174 is attached to the inner surface ofhollow shaft 172 by a suitable adhesive. In the embodiment shown inFIGS. 2K and 2L, the inner surface of hollow shaft 172 comprises a notch186. An outer region of hollow body 176 of dome valve 174 is locked innotch 186 as shown to attach dome valve 174 to hollow shaft 172. Domevalve 174 may be made from suitable biocompatible materials including,but not limited to elastomeric materials such as silicone,fluorosilicone, etc. In one embodiment, dome valve 174 is made from asingle piece of a suitable material.

Similarly, substance delivery devices disclosed herein may comprise avariety of valves to allow a user to fill a substance reservoir locateddistal to the valves while preventing unwanted drainage of the fluidsubstance from the substance reservoir. Examples of such valves include,but are not limited to cross slit valves, umbrella valves, combinationsof umbrella valve and duck-bill valve, valve balls, etc.

The shafts of the substance delivery devices disclosed herein maycomprise various filling mechanisms to fill one or more substancereservoirs located distal to the filling mechanisms without leakage ofthe substance from the shafts. Such filling mechanisms may comprise aself-sealing membrane located proximal to the substance reservoirs. Forexample, FIGS. 2M and 2N show longitudinal sections through the fillingmechanism of an embodiment of a substance delivery device comprising aself-sealing membrane. Substance delivery device 190 of FIGS. 2M and 2Ncomprises a hollow shaft 104. Hollow shaft 104 encloses a reservoirfilling lumen. A proximal region of the lumen of hollow shaft 104 isplugged by a self sealing membrane 192. Self-sealing membrane 192 may bemade of suitable biocompatible materials including, but not limited tosilicone elastomers. Substance delivery device 190 further comprises asubstance reservoir located distal to self sealing membrane 192. In FIG.2M, substance delivery device 190 is introduced into the anatomy. In theembodiment shown in FIGS. 2M and 2N, substance delivery device 190 isintroduced into the anatomy by a proximal shaft 110 that pushes hollowshaft 104 in the distal direction. Proximal shaft 110 comprises a lumen.An injecting device 194 is introduced through the lumen of proximalshaft 110. The distal tip of injecting device 194 punctures self-sealingmembrane 192 and enters the region distal to self-sealing membrane 192.Self-sealing membrane 192 allows the passage of injecting device 194while maintaining a substantial fluid seal around injecting device 194.Injecting device 194 may thereafter be used to introduce a fluidsubstance in the region distal to self-sealing membrane 192. Thus,injecting device 194 may be used to fill a substance reservoir locateddistal to self-sealing membrane 192. In FIG. 2N, injecting device 194 ispulled in the proximal direction and removed from self-sealing membrane192. The area where injecting device 194 had punctured self-sealingmembrane 192 seals itself due to the self-sealing property ofself-sealing membrane 192. This prevents unwanted drainage of the fluidsubstance through the proximal end of hollow shaft 104.

The substance delivery devices disclosed herein may comprise variousplugging mechanisms to plug a lumen of a filling lumen after filling asubstance reservoir through the filling lumen. For example, FIGS. 2O and2P show longitudinal sectional views of a region of an embodiment of asubstance delivery device comprising a plugging mechanism. Substancedelivery device 196 of FIGS. 2O and 2P comprises an elongate shaft 104enclosing a reservoir filling lumen. The filling lumen may be used tofill one or more substance reservoirs located in the distal region ofelongate shaft 104. A proximal region of elongate shaft 104 comprises aport 198 enclosing a lumen. In one embodiment, port 198 is made bylocally reducing the diameter of elongate shaft 104. In anotherembodiment, port 198 is made of suitable biocompatible materialsincluding, but not limited to silicone rubber, thermoplastic elastomers,etc. An injecting tube 200 is inserted through port 198. The outerdiameter of injecting tube 200 is approximately equal to the innerdiameter of the lumen enclosed by port 198. This creates a substantialfluid seal between the outer surface of injecting tube 200 and the innersurface of the lumen enclosed by port 198. Injecting tube 200 encloses alumen that is in fluid communication with the exterior of injecting tube200 through an opening or pore 202. The distal end of the lumen ofinjecting tube 200 is plugged by a suitable plug 204. Plug 204 isfrictionally attached to a surface of injecting tube 200. The outerdiameter of plug 204 is greater than the inner diameter of the lumenenclosed by port 198. Plug 204 may be made of suitable biocompatiblematerials including, but not limited to silicone rubber, thermoplasticelastomers, etc. In FIG. 2O, substance delivery device 196 is introducedinto the anatomy. In the embodiment shown in FIGS. 2O and 2P, substancedelivery device 196 is introduced into the anatomy by a proximal shaft110 that pushes elongate shaft 104 in the distal direction. In FIG. 2O,a user injects a fluid substance through injecting device 200 in theregion distal to port 198. This step may be used to fill a substancereservoir located distal to port 198. In FIG. 2P, the user pullsinjecting device 200 in the proximal direction. This causes plug 204 toplug the lumen enclosed by port 198 as shown in FIG. 2P. When injectingdevice 200 is pulled further in the proximal direction, plug 204detaches from injecting device 200. Thus the proximal end of the fillinglumen is plugged by plug 204. This prevents or reduces leakage of thefluid substance through the proximal end of the filling lumen.Similarly, various other embodiments of plugging mechanisms may be usedto prevent or reduce leakage of the fluid substance through the proximalend of the filling lumen.

In an alternate embodiment, plug 204 is located on the inner surface ofthe filling lumen of elongate shaft 104. Plug 204 comprises a swellablematerial that swells and increase in volume on coming into contact withthe fluid substance. Plug 204 then occludes the filling lumen ofelongate shaft 104 thereby preventing the leakage of the fluid substancefrom the proximal end of elongate shaft 104.

The substance delivery devices disclosed herein may be introduced intothe anatomy by a variety of introducing devices comprising means forcontrollably deploying the substance delivery devices from theintroducing devices. For example, FIGS. 3A and 3B show a longitudinalsection through a proximal region of a substance delivery devicedeployed by a pushing tube similar to pushing tube 114 of FIG. 1. FIG.3A shows the proximal region of a substance delivery device 100. In theembodiment substance delivery device comprises an elongate shaft 104comprising a reservoir filling lumen. Elongate shaft 104 may beconstructed from suitable biocompatible materials including, but notlimited to metals, polymers, etc. The proximal region of elongate shaft104 slides over the distal region of an elongate shaft 110 of anintroducing device 102. The inner surface of elongate shaft 104frictionally attaches to the outer surface of elongate shaft 110. Thisfrictional attachment is strong enough to prevent detachment ofsubstance delivery device 100 from introducing device 102 whileinserting and navigating substance delivery device 100 through theanatomy. A pushing tube 114 slides on the outer surface of elongateshaft 110 proximal to the proximal end of elongate shaft 104. Pushingtube 114 can be moved over the outer surface of elongate shaft 110 by auser. In the step of deploying substance delivery device 100 fromintroducing device 102, the user pushes pushing tube 114 over the outersurface of elongate shaft 110 in the distal direction as shown in FIG.3B. The distal end of pushing tube 114 pushes the proximal end ofelongate shaft 104 to overcome the frictional attachment between theinner surface of elongate shaft 104 and the outer surface of elongateshaft 110. This causes elongate shaft 104 to be released from elongateshaft 110. Thereby, substance delivery device 100 is deployed fromintroducing device 102.

In an alternate means for controllably deploying the substance deliverydevices, a substance delivery device is deployed by withdrawing afilling device from the substance delivery device. Three embodiments ofthis mechanism are illustrated in FIGS. 2K-2L, 2M-2N and 2O-2P.

In an alternate means for controllably deploying the substance deliverydevices, the substance delivery devices are deployed by cutting orsevering a region of the substance delivery devices. This causes theportion of the substance delivery device distal to the severed region tobe deployed in the anatomy.

The various methods and devices disclosed herein may be used to deliveryone or more substances to various regions in the head and neck as shownin FIGS. 4A-4E and 4A′-4E′. Examples of such regions include, but arenot limited to paranasal sinuses, Eustachian tubes, middle ear regions,etc. FIGS. 4A through 4E show a coronal view of a human head showing thevarious steps of a method of delivering an implantable substancedelivery device to one of the paranasal sinuses of a patient. In thisexample, a frontal sinus FS is used as an example of a paranasal sinus.Methods similar to those shown in FIGS. 4A through 4E may be used todeliver a substance delivery device in other paranasal sinuses or otherspaces or cavities in the head. The substance delivery devices may beintroduced along introducing devices such as guidewires, guidecatheters, etc. For example, in FIG. 4A, a guidewire GW is introducedthrough a nostril of the patient. The distal end of the guidewire isnavigated through the anatomy such that the distal end of the guidewireenters a paranasal sinus. This may be done by one or more methodsdisclosed in U.S. patent application Ser. Nos. 10/829,917; 10/912,578;11/037,548 and i0/944,270, the entire disclosures of which are expresslyincorporated herein by reference. Thereafter, in FIG. 4B, a substancedelivery device 100 is introduced over the guidewire GW into the frontalsinus. In the embodiment shown in FIG. 4B, substance delivery device 100comprises an elongate shaft 104 and a substance reservoir 106. In theexample shown, substance delivery device 100 comprises a rapid exchangelumen which allows substance delivery device 100 to be introduced overguidewire GW. Alternatively substance delivery device 100 may comprisean end-to-end guidewire lumen. In FIG. 4B, the proximal end of substancedelivery device 100 is connected to the distal end of a removabledelivery catheter 102. In the embodiment shown, delivery and inflationdevice 114 comprises an elongate tube 114 comprising a lumen. The distalend of the lumen of elongate tube 114 is in fluid communication with theproximal end of a substance introducing lumen in elongate shaft 104. Theproximal end of the lumen of elongate tube 114 is in fluid communicationwith a hub 112. A suitable syringe can be connected to hub 112 to injecta substance into reservoir 106 of substance delivery device 100. In thestep shown in FIG. 4C, the guidewire GW is removed from the anatomy. Inthe step shown in FIG. 4D, reservoir 106 is filled with a substancethrough a syringe connected to hub 112. In the step shown in FIG. 4E,the proximal end of substance delivery device 100 is detached from thedistal end of delivery catheter 102 thereby implanting substancedelivery device 100 in the anatomy. Thereafter, delivery catheter 102 isremoved from the anatomy. Substance delivery device 100 may be placed inthe anatomy for a period ranging from 0.5 hours to 60 days after whichit may be removed.

In another example, FIGS. 4A′ through 4E′ show a coronal view of a humanhead showing the various steps of an embodiment of a method ofdelivering an implantable substance delivery device to a Eustachian tubeor middle ear of a patient. The method is performed by inserting asubstance delivery device through the pharyngeal ostium of theEustachian tube. Methods similar to those shown in FIGS. 4A′ through 4E′may be used to deliver one or more substances to the Eustachian tubes orvarious regions of the middle or inner ear of patients. Examples of suchinner ear regions include, but are not limited to cochlea, vestibule,etc. The substance delivery devices may be introduced along introducingdevices such as guidewires, guide catheters, etc. For example, in FIG.4A′, a guidewire GW is introduced through a nostril of the patient. Thedistal end of the guidewire is navigated through the anatomy such thatthe distal end of the guidewire enters a Eustachian tube through thepharyngeal ostium of the Eustachian tube. This may be done by one ormore methods disclosed in U.S. patent application Ser. Nos. 10/829,917;10/912,578; 11/037,548 and i0/944,270, the entire disclosures of whichare expressly incorporated herein by reference. In a particularembodiment, the guidewire GW is introduced through a guide catheter.Thereafter, in FIG. 4B′, a substance delivery device 100 is introducedover the guidewire GW into the Eustachian tube. In the embodiment shownin FIG. 4B′, substance delivery device 100 comprises an elongate shaft104 and a reservoir 106. In the example shown, substance delivery device100 comprises a rapid exchange lumen which allows substance deliverydevice 100 to be introduced over guidewire GW. Alternatively substancedelivery device 100 may comprise an end-to-end guidewire lumen. In FIG.4B′, the proximal end of substance delivery device 100 is connected tothe distal end of a removable delivery catheter 102. In the embodimentshown, delivery catheter 102 comprises an elongate tube 114 comprising alumen. The distal end of the lumen of elongate tube 114 is in fluidcommunication with the proximal end of a substance introducing lumeninelongate shaft 104. The proximal end of the lumen of elongate tube 114is in fluid communication with a hub 112. A suitable syringe can beconnected to hub 112 to inject a substance into reservoir 106 ofsubstance delivery device 100. In the step shown in FIG. 4C′, theguidewire GW is removed from the anatomy. In the step shown in FIG. 4D′,reservoir 106 is filled with a substance through a syringe connected tohub 112. In the step shown in FIG. 4E, the proximal end of substancedelivery device 100 is detached from the distal end of delivery catheter102 thereby implanting substance delivery device 100 in the anatomy.Thereafter, delivery catheter 102 is removed from the anatomy. Substancedelivery device 100 may be placed in the anatomy for a period rangingfrom 0.5 hours to 60 days after which it may be removed.

Similar methods may be used to deliver a substance delivery device to anaso-lachrymal duct of a human or animal subject to deliver a substanceto the naso-lachrymal duct.

The guidewires disclosed herein may comprise one or more anchors totemporarily anchor the guidewires to an anatomical region. Examples ofsuch anchors include, but are not limited to anchoring balloons, notcheson the guidewires, bent regions on the guidewires, self expandingelements, hooks, coiled elements, etc. The guidewires disclosed hereinmay comprise one or more sensors located on the distal region of theguidewires. The sensors enable the guidewires to be used in conjunctionwith suitable surgical navigation systems. In one embodiment, the sensoris an electromagnetic sensor used in conjunction with an electromagneticsurgical navigation system such as GE InstaTrak™ 3500 plus system etc.One or more sensors or other types of surgical navigation sensors ortransmitters may also be located on other diagnostic or therapeuticdevices disclosed herein.

The various substance reservoirs disclosed herein may be inflatable ornon-inflatable. Inflatable substance reservoirs may be made of suitableballoons. The balloons may be made of various shapes including, but notlimited to the balloon shapes disclosed herein and in the patentdocuments incorporated herein by reference. The balloons may be designedto also function as anchoring mechanisms to anchor the substancereservoir to the anatomy. Such anchoring is especially useful when thesubstance reservoirs are inserted into hollow regions such as paranasalsinuses. FIGS. 4F through 4L show various embodiments of substancereservoirs that can be used to design the various substance deliverydevices disclosed herein. FIG. 4F shows a perspective view of anembodiment of an inflatable substance reservoir comprising an inflatableballoon comprising two or more lobes. FIG. 4F shows a region of asubstance delivery device 210 comprising an inflatable balloon 212comprising two or more lobes 214. Such a balloon shape comprising two ormore lobes is useful to allow drainage of secretions when the balloon isplaced in an anatomical region. For example, when inflatable balloon 212is placed in a paranasal sinus through an ostium of the paranasal sinus,lobes 214 allows sinus secretions to flow between the lobes of theballoon and out of the ostium of the paranasal sinus. Inflatable balloon212 may be made of suitable compliant, non-compliant or semi-compliantbiocompatible materials. Examples of such materials include, but are notlimited to polyurethane, silicone, Nylon, PET, polyethylene, PVC, etc.Inflatable balloon 212 is inflated by a substance introducing lumen inelongate shaft 104. FIG. 4G shows a cross section of inflatable balloon212 shown in FIG. 4F through the plane 4G-4G. FIG. 4G shows inflatableballoon 212 comprising multiple lobes 214. In the example shown in FIGS.4F and 4G, the substance reservoir comprised a balloon having 10 lobes.Similarly other substance reservoirs may be designed comprising aballoon having two or more lobes.

FIG. 4H shows a perspective view of an embodiment of an inflatablesubstance reservoir comprising a spiral inflatable balloon. FIG. 4Fshows a region of a substance delivery device 218 comprising a spiralinflatable balloon 220. Such a spiral balloon is useful to allowdrainage of secretions when the balloon is placed in an anatomicalregion. For example, when the balloon is placed in a paranasal sinusthrough an ostium of the paranasal sinus, a spiral balloon allows sinussecretions to flow between adjacent turns of the spiral balloon and outof the ostium of the paranasal sinus. Inflatable balloon 220 may be madeof suitable compliant, non-compliant or semi-compliant biocompatiblematerials. Examples of such materials include, but are not limited topolyurethane, silicone, Nylon, PET, polyethylene, PVC, etc. Inflatableballoon 220 is inflated by an elongate shaft 104.

The inflatable substance reservoirs disclosed herein may comprise one ormore radial protrusions. For example, FIG. 4I shows a perspective viewof a region of a substance delivery device comprising an inflatableballoon having one or more radial protrusions. Substance delivery device222 comprises an inflatable balloon 224. The inflatable balloon 224comprises one or more radial protrusions 226. Radial protrusions 226 areoriented radially to the axis of inflatable balloon 224. Radialprotrusions 226 may be inflatable or non-inflatable. This increases theprofile of inflatable balloon 224 when inflatable balloon 224 isinflated. Such a balloon comprising one or more radial protrusions isuseful to allow drainage of secretions when the balloon is placed in ananatomical region. For example, when balloon 224 is placed in aparanasal sinus through an ostium of the paranasal sinus, balloon 224allows sinus secretions to flow between adjacent protrusions 226 and outof the ostium of the paranasal sinus. Protrusions 226 also help toanchor balloon 224 to the surrounding anatomy. Inflatable balloon 224may be made of suitable compliant, non-compliant or semi-compliantbiocompatible materials. Examples of such materials include, but are notlimited to polyurethane, silicone, Nylon, PET, polyethylene, PVC, etc.Inflatable balloon 224 is inflated by a substance introducing lumeninelongate shaft 104.

The inflatable substance reservoirs disclosed herein may comprise aballoon oriented transversely to the axis of an inflating shaft. Forexample, FIG. 4J shows a perspective view of a region of a substancedelivery device comprising an inflatable balloon oriented transverselyto the axis of the substance delivery device. In FIG. 4J, a substancedelivery device 228 is inserted through a paranasal sinus ostium into aparanasal sinus. Substance delivery device 228 comprises an elongateinflatable balloon 230. The axis of inflatable balloon is substantiallyperpendicular to the axis of substance delivery device 228. Thisincreases the profile of inflatable balloon 230 when inflatable balloon230 is inflated. This helps to anchor balloon 242 to the surroundinganatomy while still allowing secretions to flow around balloon 230.Inflatable balloon 230 may be made of suitable compliant, non-compliantor semi-compliant biocompatible materials. Examples of such materialsinclude, but are not limited to polyurethane, silicone, Nylon, PET,polyethylene, PVC, etc. Inflatable balloon 230 is inflated by asubstance introducing lumen in elongate shaft 231.

The inflatable substance reservoirs disclosed herein may comprise aballoon having one or more vents to prevent vacuum formation inside asubstance reservoir. For example, FIG. 4K shows a side view of a regionof an inflatable substance reservoir comprising a balloon with one ormore pores and a vent. FIG. 4K shows a substance delivery device 232comprising an inflatable balloon 234 that acts as a substance reservoir.Inflatable balloon 234 may be made of suitable non-compliant orsemi-compliant biocompatible materials. Examples of such materialsinclude, but are not limited to polyurethane, Nylon, PET, polyethylene,PVC, etc. Inflatable balloon 234 is inflated by an elongate shaft 104comprising a reservoir filling lumen. The lumen of elongate shaft 104 isin fluid communication with inflatable balloon 234. Inflatable balloon234 comprises one or more pores 236. The substance stored in inflatableballoon 234 is delivered through pores 236 into the surrounding anatomy.Thus, the volume of the substance stored in inflatable balloon 234gradually reduces. This process gradually creates a vacuum insideinflatable balloon 234. The vacuum prevents or reduces the delivery ofthe substance stored in inflatable balloon 234 through pores 236. Inorder to prevent or reduce the formation of the vacuum, substancedelivery device 232 further comprises a vent 238. Vent 238 allows air toenter inflatable balloon 234. This air replaces the amount of substancelost through pores 236 and thus prevents the formation of a vacuum ininflatable balloon 234. This in turn maintains the rate of delivery ofthe substance stored in inflatable balloon 234 through pores 236.

The distal end of one or more substance delivery devices disclosedherein may be designed to prevent or reduce trauma to the surroundinganatomy. In the embodiments of substance delivery devices comprising aninflatable substance reservoir, a portion of the inflatable reservoirmay be designed to generate an atraumatic distal region. For example,FIG. 4L shows a section through a substance delivery device comprisingan inflatable substance delivery reservoir shaped to produce anatraumatic distal end. In FIG. 4L, substance delivery device 240comprises an inflatable balloon 242 that acts as a substance reservoir.Inflatable balloon 242 may be made of suitable compliant, non-compliantor semi-compliant biocompatible materials. Examples of such materialsinclude, but are not limited to polyurethane, silicone, Nylon, PET,polyethylene, PVC, etc. Inflatable balloon 242 is inflated through anelongate shaft 104 comprising a reservoir filling lumen. The lumen ofelongate shaft 104 is in fluid communication with balloon 242 through ashaft opening 244. A distal region of elongate shaft 104 is plugged orblocked by a plug 246. Inflatable balloon 242 may further comprise oneor more pores 248 that are in fluid communication with the exterior ofinflatable balloon 242. Substance delivery device 240 may deliver asubstance to the surrounding anatomy through pores 248. Inflatableballoon 242 is connected to elongate shaft 104 at a proximal region andat a distal region of inflatable balloon 242. The distal region ofinflatable balloon 242 is everted and connected to elongate shaft 104 asshown in FIG. 4L. Thus, when inflatable balloon 242 is inflated, adistal region of inflatable balloon 104 protrudes distal to the distalend of elongate shaft 104 as shown in FIG. 4L. This creates anatraumatic distal end of substance delivery device 240.

The one or more pores on the inflatable substance reservoirs such as theinflatable substance reservoirs disclosed in FIGS. 4K and 4L may becreated by laser drilling the surface of the materials of the inflatablesubstance reservoirs. In one example of a method of creating the one ormore pores, an Excimer laser is used to create pores. The Excimer lasermay be used to create pores of a pore size ranging from about 20 micronsto about 200 microns. Inflatable balloon 234 and inflatable balloon 242of FIGS. 4K and 4L respectively may have a balloon diameter ranging fromaround 7-10 mm and balloon length ranging from around 10-20 mm. Theballoon wall thickness may range from around 0.001-0.003 inches. Thenumber and pore size of the one or more pores and the balloon wallthickness may be designed to avoid jetting of the substance stored inthe inflatable substance reservoirs through the one or more pores.

One or more substance delivery devices disclosed herein may comprisemore than one substance reservoirs that are inflated through one or morereservoir filling lumens. Also, one or more substance reservoirsdisclosed herein may act as anchors to prevent or reduce relative motionbetween the substance delivery devices and regions of the anatomy. Forexample, FIG. 4M shows a cross section through a substance deliverydevice comprising two substance reservoirs that also act as anchors.Substance delivery device 250 of FIG. 4M comprises an outer tube 252 andan inner tube 254 enclosed by outer tube 252. Outer tube 252 and innertube 254 may be made of suitable biocompatible materials including, butnot limited to Pebax, PEEK, Nylon, polyethylene, polyurethane,polyethylene terephthalate, etc. Inner tube 254 encloses an inner lumen256. The annular region between the outer surface of inner tube 254 andthe inner surface of outer tube 252 forms an outer lumen 258. The distalend of outer lumen 258 is plugged by an annular plug 260. Inner tube 254comprises a first opening or pore 262 located distal to the distal endof outer tube 252. First opening or pore 262 creates a fluidcommunication between inner lumen 256 and a distal balloon 264. Thus,inner lumen 256 may be used to inflate distal balloon 264 with asuitable fluid substance. A distal region of distal balloon 264 isattached to the outer surface of inner tube 254 and a proximal region ofdistal balloon 264 is attached to the outer surface of outer tube 252 asshown. A region of outer tube 252 proximal to annular plug 260 comprisesa second opening or pore 266. Second opening or pore 266 creates a fluidcommunication between outer lumen 258 and a proximal balloon 268. Thus,outer lumen 258 may be used to inflate proximal balloon 268 with asuitable fluid substance. Outer lumen 258 and inner lumen 256 may beprovided with valves, plugging mechanisms, etc. disclosed elsewhere inthis patent application to prevent the leakage of the fluid substancefrom the proximal ends of outer lumen 258 and inner lumen 256. In onemethod embodiment, substance delivery device 250 is introduced throughan anatomical opening such as a paranasal sinus ostium. Substancedelivery device 250 is positioned such that distal balloon 264 liesdistal to the anatomical opening and proximal balloon 268 lies proximalto the anatomical opening. Thereafter, both distal balloon 264 andproximal balloon 268 are inflated. Both distal balloon 264 and proximalballoon 268 acts as anchors and prevent or reduce the motion ofsubstance delivery device 250 relative to the anatomical opening. In theembodiment shown in FIG. 4M, distal balloon 262 and proximal balloon 268are inflated by two separate lumens. In an alternate embodiment, distalballoon 262 and proximal balloon 268 are inflated by a single lumen.

Although the substance reservoirs disclosed herein are mostlyillustrated as inflatable balloons, the substance delivery devicesdisclosed herein may comprise several other embodiments of substancereservoirs. For example, the substance reservoirs disclosed herein maycomprise an absorbent element. Examples of such absorbent elementsinclude, but are not limited to foams, fibrous elements, etc. FIG. 4Nshows a partial view of an embodiment of a substance delivery devicecomprising a substance reservoir made of foam. Substance delivery device270 of FIG. 4N comprises an elongate shaft 104. Elongate shaft 104comprises a reservoir filling lumen. The filling lumen is in fluidcommunication with a substance reservoir 272 located on the distalregion of elongate shaft 104. The filling lumen may be used to introducea suitable substance into substance reservoir 272 before or afterinsertion of substance delivery device 270 into the anatomy. Substancereservoir 272 may be made from suitable biocompatible foam materialsincluding, but not limited to polyvinyl acetate, polyurethane,polylactides, carboxymethylated cellulose, polyethylene, silicone,biodegradable materials such as gelatin, fibers such as cotton, etc.Substance reservoir 272 may be connected to a controlled deliveryelement. The controlled delivery element may be used to deliver thesubstance in substance reservoir 272 to the surrounding anatomy at acontrolled rate over a desired period of time. In one embodiment, thecontrolled delivery element comprises a membrane located on the outersurface of substance reservoir 272. The membrane regulates the deliveryof the substance from substance reservoir 272 to the surroundinganatomy. Substance reservoir 272 may be enclosed in a series of strutsthat contain substance reservoir 272. In one embodiment, the struts aresubstantially parallel to elongate shaft 104.

One or more of the drug delivery devices disclosed herein may comprise acontrolled substance release mechanism to controllably release asubstance from a substance reservoir into the surrounding anatomy over aperiod of time. In one embodiment, the controlled substance releasemechanism comprises a pressuring mechanism that exerts a pressure on thesubstance reservoir to squeeze the substance out of the substancereservoir into the surrounding anatomy. The pressuring mechanism may bedesigned to exert a fairly constant pressure over the treatmentduration.

One example of a pressuring mechanism is shown in FIG. 5A. FIG. 5A showsa sectional view of an embodiment of a substance delivery devicecomprising a pressure exerting mechanism. The design of substancedelivery device 276 of FIG. 5A is similar to the design of substancedelivery substance 240 of FIGS. 2G and 2H. Drug delivery device 276comprises an elongate shaft 278. Elongate shaft 278 may be made ofsuitable biocompatible materials including, but not limited to Pebax,PEEK, Nylon, polyethylene, etc. Elongate shaft 278 encloses a substanceintroducing lumen 280. A distal region of lumen 280 is blocked by a plug232. A substance reservoir 282 is located on a distal region of elongateshaft 278. In the example shown in FIG. 5A, substance delivery reservoir282 comprises an inflatable balloon. The inflatable balloon ispreferably made from suitable non-compliant, compliant or semi-compliantmaterials including, but not limited to polyurethane, silicone, Nylon,PET, polyethylene, PVC, C-flex™, etc. The material of the inflatableballoon is substantially impermeable to water. Lumen 280 is in fluidcommunication with substance reservoir 282 through one or more firstopenings or pores 284. Lumen 280 may thus be used to fill substancereservoir 282 with a suitable substance. A valve 286 is located nearfirst openings or pores 284. Valve 286 allows the substance to flow fromlumen 280 to substance reservoir 282. Also, valve 286 prevents orsubstantially reduces the flow of the substance from substance reservoir282 to lumen 280. The design of valve 286 in FIG. 5A is similar to thedesign of valve 252 in FIGS. 2G and 2H. The substance stored insubstance reservoir 282 is released into the surrounding anatomy throughone or more second openings or pores 288 that create a fluidcommunication between substance reservoir 282 and lumen 280. In theexample shown in FIG. 5A, one or more second openings or pores 288 arepresent on the region of elongate shaft 278 enclosed by substancereservoir 282. In this example, the distal end of lumen 280 opens intothe surrounding anatomy such that the substance flows from substancereservoir 282 to the surrounding anatomy. Substance delivery device 276further comprises a pressure exerting mechanism comprising a waterpermeable membrane 290 and a water-swellable material 292 enclosedwithin water permeable membrane 290. Water-swellable material 292 issandwiched between water permeable membrane 290 and the outer surface ofsubstance delivery reservoir 282 as shown in FIG. 5A. After substancedelivery device 276 is implanted in a target anatomical region such as aparanasal sinus, water molecules from the surrounding fluids e.g. sinusmucous gradually permeate through water permeable membrane 290. Thesewater molecules then come into contact with water-swellable material292. This in turn causes water-swellable material 292 to gradually swellover a period of time. FIG. 5A′ shows a sectional view of the embodimentof the substance delivery device shown in FIG. 5A showing the pressureexerting mechanism exerting a pressure on a substance reservoir.Swelling of water-swellable material 292 exerts a gradually increasingpressure on substance delivery reservoir 282 as shown in FIG. 5A′. Thisgradually squeezes substance reservoir 282 and causes the substancestored in substance reservoir 282 to be gradually released through oneor more second openings or pores 288 into the surrounding anatomy. Waterpermeable membrane 290 may be made of suitable materials that allowwater molecules to pass through but filter out dissolved or un-dissolvedsolids including the substance stored in substance reservoir 282 asshown in FIG. 5A′. Examples of such membranes include, but not limitedto reverse osmosis membranes, nanofiltration membranes, etc. Waterpermeable membrane 290 may be made of a wide variety of natural andsynthetic polymers, including, but not limited to polydimethylsiloxanes(silicone rubbers), ethylene-vinylacetate copolymers, polyurethanes,polyurethane-polyether copolymers, polyethylenes, polyamides,polyvinylchlorides (PVC), polypropylenes, polycarbonates,polytetrafluoroethylenes (PTFE), polyacrylonitriles, polysulfones,cellulosic materials (e.g., cellulose monoacetate, cellulose diacetate,cellulose triacetate, cellulose nitrate, etc.), hydrogels (e.g.,2-hydroxymethylmethacrylate), etc. In one embodiment, water-swellablematerial 292 is made of suitable super-absorbent polymers including, butnot limited to sodium salts of crosslinked polyacrylic acid, potassiumsalts of crosslinked polyacrylic acid/polyacrylamide copolymer,synthetic polyacrylamide with a potassium salt base, graft copolymers ofcross-linked polyacrylic acid and starch, SNAPs (Safe and NaturalAbsorbent Polymers), etc.

FIG. 5B shows a cross sectional view of an embodiment of a substancedelivery device comprising a controlled substance release element in theform of a wick. The basic design of substance delivery device 296 ofFIG. 5B is similar to the design of substance delivery device 240 ofFIG. 4L. Substance delivery device 296 comprises a substance reservoir.In the embodiment shown in FIG. 5B, the substance reservoir is aninflatable balloon 106. Inflatable balloon 106 may be made of suitablecompliant or semi-compliant biocompatible materials. Examples of suchmaterials include, but are not limited to polyurethane, silicone, Nylon,PET, polyethylene, PVC, etc. Inflatable balloon 106 is inflated throughan elongate shaft 104 comprising a reservoir filling lumen. Inflatableballoon 106 is connected to elongate shaft 104 at a proximal region andat a distal region of inflatable balloon 106. The distal region ofinflatable balloon 106 is everted and connected to elongate shaft 104 asshown in FIG. 5B. Thus, when inflatable balloon 106 is inflated, adistal region of inflatable balloon 106 protrudes distal to the distalend of elongate shaft 104 as shown in FIG. 5B. This creates anatraumatic distal end of substance delivery device 296. The lumen ofelongate shaft 104 is in fluid communication with inflatable balloon 106through a shaft opening 298. The lumen of elongate shaft 104 furthercomprises a plugging mechanism e.g. a one way valve. The pluggingmechanism is located proximal to shaft opening 298. The pluggingmechanism prevents the backflow of fluid along the proximal directionafter a user fills inflatable balloon 106 with a suitable fluidsubstance through the lumen of elongate shaft 104. Substance deliverydevice 296 further comprises a controlled delivery mechanism forcontrolled delivery of a substance from substance delivery device 296.In the embodiment shown in FIG. 5B, the controlled delivery mechanism isan elongate wick 300 attached to the distal end of elongate shaft 104.Wick 300 is in fluid communication with the lumen of elongate shaft 104.Wick 300 comprises a plurality of pores or channels such that a fluid incontact with the proximal region of wick 300 is transported in thedistal direction along wick 300 by capillary action. Wick 300 may bemade of suitable biocompatible polymers including, but not limited tocellulose, collagen, polyvinyl acetate, etc. Wick 300 may comprise avariety of two-dimensional or three dimensional shapes. For example,wick 300 may comprise one or more turns, coils, bends, curves or angledregions, etc. to increase the area of contact surface between wick 300and a region of the anatomy. Wick 300 regulates the delivery of thesubstance from the substance reservoir to the surrounding anatomy andthus allows for extended delivery of the substance to the surroundinganatomy. In one embodiment of a method of using substance deliverydevice 296, a user introduces substance delivery device 296 into atarget anatomical region such that one or more regions of wick 300 arein contact with the anatomical region. Thereafter, the user introduces asuitable substance in inflatable balloon 106. Thereafter, the substancein inflatable balloon 106 comes into contact with the proximal region ofwick 300. The substance is then transported along wick 300 by capillaryaction. The substance is then delivered to the anatomical region at acontrolled rate through wick 300.

In an alternate embodiment, the controlled delivery mechanism is a thinelongate delivery tube comprising a delivery lumen. The proximal end ofthe delivery lumen is in fluid communication with the substance storedin substance delivery device 296. The substance is delivered to thesurrounding anatomy from the distal tip of the delivery lumen. Thedelivery tube may comprise one or more turns, coils, bends, curves orangled regions, etc. The delivery tube regulates the delivery of thesubstance from the substance reservoir to the surrounding anatomy andthus allows for extended delivery of the substance to the surroundinganatomy.

One or more embodiments of substance delivery devices disclosed hereinmay comprise various embodiments of porous elements for controlling therate of delivery of a substance to the anatomy. Such porous elements maycomprise one or more pores. The pore size of such pores may range from0.2 microns to 200 microns. For example, FIG. 5C shows the side view ofan embodiment of an elongate porous tube 302 that may be used to controlthe rate of delivery of a substance to the anatomy from a substancedelivery device. Porous tube 302 comprises an elongate tube comprising alumen. The elongate tube may be made of suitable biocompatible materialsincluding, but not limited to silicone, Pebax, PEEK, Nylon,polyethylene, polyurethane, etc. The elongate tube comprises one or morepores that create a fluid communication between the exterior of poroustube 302 and the lumen of porous tube 302. The one or more pores mayhave a pore size ranging from 0.2 microns to 200 microns. The proximalend of porous tube 302 is plugged by a plug 304. An atraumatic tip 306may be attached to the distal end of porous tube 302 to prevent orreduce damage to the anatomy by the distal end of porous tube 302.

FIG. 5D shows a cross sectional view of an embodiment of a substancedelivery device comprising the porous tube 302 of FIG. 5C. Substancedelivery device 308 comprises a substance reservoir. In the embodimentshown in FIG. 5D, the substance reservoir is an inflatable balloon 106.Inflatable balloon 106 may be made of suitable compliant orsemi-compliant biocompatible materials. Examples of such materialsinclude, but are not limited to polyurethane, silicone, Nylon,polyethylene, PVC, etc. inflatable balloon 106 is inflated through anelongate shaft 310 comprising a reservoir filling lumen. Elongate shaft310 comprises a proximal opening 312 that creates a fluid communicationbetween the lumen of elongate shaft 310 and inflatable balloon 106. Thelumen of elongate shaft 310 further comprises a plugging mechanism e.g.a one way valve. The plugging mechanism is located proximal to proximalopening 312. The plugging mechanism prevents the backflow of fluid alongthe proximal direction after a user fills inflatable balloon 106 with asuitable fluid substance through the lumen of elongate shaft 310.Elongate shaft 310 further comprises a distal opening 314 that createsanother fluid communication between the lumen of elongate shaft 310 andinflatable balloon 106. Distal opening 314 is located distal to proximalopening 312 as shown in FIG. 5D. The inner diameter of the lumen ofelongate shaft 310 is slightly larger than the outer diameter of poroustube 302. This allows porous tube 302 to be inserted into elongate shaft310 through the distal end of elongate shaft 310 as shown in FIG. 5D.Porous tube 302 is positioned relative to elongate shaft 310 such thatplug 304 is located between distal opening 314 and proximal opening 312.Thereafter, porous tube 302 is attached to elongate shaft 310. A fluidsubstance present in inflatable balloon 106 can flow through distalopening 314 and thereafter through the walls of porous tube 302 andthereafter through the distal end of porous tube 302. Thus, substancedelivery device 308 can be used to deliver a fluid substance to thesurrounding anatomy at a controlled rate that is controlled by thedesign of porous tube 302. Substance delivery device 308 may adapted tobe inserted into an anatomical region such as a paranasal sinus along anintroducing device. Examples of such introducing devices include, butare not limited to guidewires, guide catheters, etc. In the exampleshown in FIG. 5D, substance delivery device 308 further comprises asecond elongate shaft 316 comprising a lumen. Second elongate shaft 316is attached to elongate shaft 310 such that second elongate shaft 316 issubstantially parallel to elongate shaft 310. The lumen of secondelongate shaft 316 acts as a rapid-exchange lumen to allow a user toadvance substance delivery device 316 into the anatomy over a suitableguidewire.

FIG. 5E shows a cross sectional view of an embodiment of a substancedelivery device comprising a porous shaft region for controlled deliveryof a substance to the anatomy. Substance delivery device 318 comprises asubstance reservoir. In the embodiment shown in FIG. 5E, the substancereservoir is an inflatable balloon 106. Inflatable balloon 106 may bemade of suitable compliant or semi-compliant biocompatible materials.Examples of such materials include, but are not limited to polyurethane,silicone, Nylon, polyethylene, PVC, etc. Inflatable balloon 106 isinflated through an elongate shaft 104 comprising a substanceintroducing lumen 320. The distal end of elongate shaft 104 terminateswithin inflatable balloon 106 to create a fluid communication betweenthe lumen 320 and inflatable balloon 106. Lumen 320 may be used tointroduce a fluid substance into inflatable balloon 106. Lumen 320further comprises a plugging mechanism e.g. a one way valve. Theplugging mechanism prevents the backflow of fluid along the proximaldirection after a user fills inflatable balloon 106 with a suitablefluid substance through lumen 320. Substance delivery device 318 mayadapted to be inserted into an anatomical region such as a paranasalsinus along an introducing device. Examples of such introducing devicesinclude, but are not limited to guidewires, guide catheters, etc. In theexample shown in FIG. 5E, substance delivery device 318 furthercomprises a second elongate shaft 124 comprising a lumen 322. A regionof second elongate shaft 124 is attached to elongate shaft 104 such thatsecond elongate shaft 124 is substantially parallel to elongate shaft104. Thus, lumen 322 can be used as a rapid-exchange lumen to allow auser to advance substance delivery device 318 into the anatomy over asuitable guidewire. Substance delivery device 318 further comprises athird elongate shaft 324. Third elongate shaft 324 is coaxial to secondelongate shaft 124 as shown in FIG. 5E. Third elongate shaft 324 may bemade of suitable biocompatible materials including, but not limited tosilicone, Pebax, PEEK, Nylon, polyethylene, polyurethane, etc. Thirdelongate shaft 324 and second elongate shaft 124 enclose a lumen 328.The proximal end of lumen 328 is plugged with an annular plug 326 asshown in FIG. 5E. Third elongate shaft 324 comprises one or more poresthat create a fluid communication between inflatable balloon 106 andlumen 328. The one or more pores may have a pore size ranging from 0.2microns to 200 microns. A fluid substance present in inflatable balloon106 can flow through the porous walls of third elongate shaft 324 andthereafter through the distal end of lumen 328. Thus, substance deliverydevice 318 can be used to deliver a fluid substance to the surroundinganatomy at a controlled rate that is controlled by the porous walls ofthird elongate shaft 324.

FIG. 5F shows a cross section of the substance delivery device of FIG.5E through the plane 5F-5F. FIG. 5F shows second elongate shaft 124enclosing lumen 322. Also shown is third elongate shaft 324 coaxial tosecond elongate shaft 124. Third elongate shaft 324 and second elongateshaft 124 enclose lumen 328.

In an alternate embodiment, the controlled substance release mechanismcomprises a diffusion barrier. The diffusion barrier is in fluidcommunication with a substance stored in a substance reservoir. Thesubstance diffuses through the diffusion barrier and into thesurrounding over a period of time.

The substance delivery devices disclosed herein may comprise one or moreanchoring or retention elements to secure the position of the substancedelivery devices relative to the anatomy. In some embodiments, the oneor more substance reservoirs may act as the anchoring or retentionelements. For example, in one embodiment of a substance delivery devicecomprising an inflatable substance reservoir, the inflatable substancereservoir is located within a paranasal sinus. The size of the inflatedinflatable substance reservoir is greater than the size of the ostium ofthe paranasal sinus. This prevents or minimizes the risk of theinflatable substance reservoir sliding out of the paranasal sinus. Theinflatable substance reservoir may comprise a shape specially designedto prevent or minimize the risk of the inflatable substance reservoirsliding out of the paranasal sinus. Examples of such shapes include, butare not limited to the inflatable reservoir shapes shown in FIGS. 4F-4J.

The one or more anchoring or retention elements may be present on theshafts of the substance delivery devices disclosed herein. Examples ofsuch anchoring or retention elements are shown in FIGS. 6A-6E′. FIG. 6Ashows an embodiment of a substance delivery device comprising ananchoring or retention element comprising deployable arms. Substancedelivery device 334 of FIG. 6A comprises an elongate shaft 104 connectedto a substance reservoir 106. Substance delivery device 334 furthercomprises an outer sheath 336 that slides over elongate shaft 104. Oneor more deployable arms 338 are connected to outer sheath 336 andelongate shaft 104. In the embodiment shown in FIG. 6A, substancedelivery device 334 comprises two deployable arms 338. Each deployablearm 338 comprises a bent, curved or angled region. The distal end ofeach deployable arm 338 is connected to elongate shaft 104. The proximalend of each deployable arm 338 is connected to a distal region of outersheath 336. Deployable arms 338 may be made of suitable elasticmaterials including, but not limited to metals such as Nitinol,stainless steel, etc.; polymers such as Nylon, PET, Pebax, PEEK, etc.Deployable arms 338 assume a bent configuration in the relaxed state. Inthis configuration, a bent region of deployable arms 338 extends in aradially outward direction as shown in FIG. 6A′. This increases theprofile of substance delivery device 334, thereby preventing substancedelivery device 334 from slipping out of an anatomical region such as aparanasal sinus. A user can temporarily reduce the profile of substancedelivery device 334 by pulling outer sheath 336 in the proximaldirection relative to elongate shaft 104. This causes deployable arms338 to get stretched along the axis of substance delivery device 334,thereby reducing the profile of substance delivery device 334. Substancedelivery device 334 can be inserted into or removed from an anatomicalregion in this configuration. FIG. 6A′ shows substance delivery device334 of FIG. 6A deployed in a sphenoid sinus.

FIG. 6B shows a perspective view of an embodiment of a substancedelivery device comprising a bent or angled shaft. Substance deliverydevice 340 of FIG. 6B comprises an elongate shaft 342 connected to asubstance reservoir 106. Elongate shaft 342 may be made of suitableelastic materials including, but not limited to Pebax, Nylon,polyethylene, etc. A region of elongate shaft 342 comprises a bent orangled region as shown in FIG. 6B. The bent or angled region increasesthe profile of substance delivery device 340, thereby preventingsubstance delivery device 340 from slipping out of an anatomical regionsuch as a paranasal sinus. A user may temporarily reduce the profile ofsubstance delivery device 340 by using a suitable device such as astylet, guidewire, guide catheter, etc. to temporarily straightenelongate shaft 342. The user may then introduce substance deliverydevice 340 into a region of the anatomy. The user may remove substancedelivery device 340 from the anatomy by pulling elongate shaft 342 inthe proximal direction with a force sufficient to cause elongate shaft342 to temporarily straighten. FIG. 6B′ shows substance delivery device340 of FIG. 6B deployed in a sphenoid sinus.

FIG. 6C shows a perspective view of an embodiment of a substancedelivery device comprising a shaft comprising a curved or coiled region.Substance delivery device 344 of FIG. 6C comprises an elongate shaft 346connected to a substance reservoir 624. Elongate shaft 346 may be madeof suitable elastic materials including, but not limited to Pebax,Nylon, polyethylene, etc. A region of elongate shaft 346 comprises acurved or coiled region as shown in FIG. 6C. The curved or coiled regionincreases the profile of substance delivery device 344, therebypreventing substance delivery device 344 from slipping out of ananatomical region such as a paranasal sinus. A user may temporarilyreduce the profile of substance delivery device 344 by using a suitabledevice such as a stylet, guidewire, guide catheter, etc. to temporarilystraighten elongate shaft 342. The user may then introduce substancedelivery device 344 into a region of the anatomy. The user may removesubstance delivery device 344 from the anatomy by pulling elongate shaft346 in the proximal direction with a force sufficient to cause elongateshaft 346 to temporarily straighten. FIG. 6C′ shows substance deliverydevice 344 of FIG. 6C deployed in a sphenoid sinus.

FIG. 6D shows a perspective view of an embodiment of a substancedelivery device comprising an elongate shaft comprising flexible,projections. Substance delivery device 348 of FIG. 6D comprises anelongate shaft 104 connected to a substance reservoir 106. Elongateshaft 104 may be made of suitable materials including, but not limitedto metals such as Nitinol, stainless steel, etc.; polymers such asNylon, PET, Pebax, PEEK, polyethylene, silicone, etc. A region ofelongate shaft 104 comprises one or more projections or arms 350. Theone or more projections or arms 350 may be made of suitable flexible,biocompatible materials including, but not limited to metals such asNitinol, stainless steel, etc.; polymers such as Nylon, PET, Pebax,PEEK, polyethylene, silicone, etc. The one or more projections or arms350 extend in a radially outward direction from elongate shaft 104. Thisincreases the profile of substance delivery device 348. Substancedelivery device 348 may be inserted through an anatomical opening bypushing substance delivery device 348 with a sufficient force in thedistal direction. This force bends the one or more projections or arms350 and thus reduces the profile of substance delivery device 348. Aftersubstance delivery device 348 is inserted through the anatomicalopening, the one or more projections or arms 350 extend in a radiallyoutward direction and prevent slipping of substance delivery device 348out of the anatomical opening. Substance delivery device 348 may beremoved through the anatomical opening by pulling substance deliverydevice 348 with a sufficient force in the proximal direction. FIG. 6D′shows substance delivery device 348 of FIG. 6D deployed in a sphenoidsinus.

The substance delivery devices disclosed herein may comprise one or moreanchoring or retention elements located on the substance reservoirs.Such anchoring or retention elements help to secure the position of thesubstance delivery devices relative to the anatomy. Such anchoring orretention elements may also help to maintain a particular position ofthe substance reservoir relative to an anatomical region to allow thenatural flow of anatomical fluids around the substance reservoirs. Forexample, FIG. 6E shows a perspective view of an embodiment of asubstance delivery device comprising a substance reservoir having one ormore radial projections. Substance delivery device 352 of FIG. 6Ecomprises an elongate shaft 104 connected to a substance reservoir 106.Elongate shaft 104 may be made of suitable materials including, but notlimited to metals such as Nitinol, stainless steel, etc.; polymers suchas Nylon, PET, Pebax, PEEK, polyethylene, silicone, etc. Substancereservoir 106 comprises one or more radial projections or arms 354. Theone or more projections or arms 354 may be made of suitable flexible,biocompatible materials including, but not limited to polymers such asNylon, PET, Pebax, PEEK, polyethylene, silicone, etc. The one or moreprojections or arms 354 extend in a radially outward direction substancereservoir 106. This increases the profile of substance reservoir 106after substance reservoir 106 is filled with a suitable substance.Substance delivery device 352 may be inserted through an anatomicalopening by pushing substance delivery device 352 with a sufficient forcein the distal direction. Thereafter, substance reservoir 106 is filledwith a suitable substance. One or more projections or arms 354 extend ina radially outward direction and prevent slipping of substance deliverydevice 352 out of the anatomical opening. FIG. 6E′ shows substancedelivery device 352 of FIG. 6E deployed in a sphenoid sinus. In FIG.6E′, projections or arms 354 cause substance reservoir 352 to bepositioned at a particular distance away from the sphenoid sinus ostiumSSO. This prevents substance reservoir 354 from blocking the naturalflow of mucous through the sphenoid sinus ostium.

The substance delivery devices disclosed herein may be sutured to ananatomical region to secure the position of the substance deliverydevices relative to the anatomical region. This may be achieved bypassing a suture through one or more suturing arrangements present onthe substance delivery devices. Examples of such suturing arrangementsare shown in FIGS. 6F-6H.

FIG. 6F shows a perspective view of an embodiment of a substancedelivery device comprising a suturing arrangement comprising a loop.Substance delivery device 358 of FIG. 6F comprises an elongate shaft 104and a substance reservoir 106 located on the distal region of shaft 104.Shaft 104 further comprises a loop 360. A user can pass a suitablesuture 362 through loop 360 and secure substance delivery device 358 toan anatomical region. Suture 362 may be biodegradable ornon-biodegradable.

FIG. 6G shows a perspective view of an embodiment of a substancedelivery device comprising a suturing arrangement comprising anaperture. Substance delivery device 358 of FIG. 6G comprises an elongateshaft 104 and a substance reservoir 106 located on the distal region ofshaft 104. Shaft 104 further comprises one or more apertures 364. In theembodiment shown in FIG. 6G, the one or more apertures 364 are locatedon a rectangular tab 365 attached to a region of shaft 104. A user canpass a suitable suture 362 through one or more apertures 364 and securesubstance delivery device 363 to an anatomical region. In an alternateembodiment, one or more apertures 364 are located on a region of shaft104. Suture 362 may be biodegradable or non-biodegradable.

FIG. 6H shows a perspective view of an embodiment of a substancedelivery device comprising a suturing arrangement comprising a coiled,twisted or bent region. Substance delivery device 366 of FIG. 6Hcomprises an elongate shaft 104 and a substance reservoir 106 located onthe distal region of shaft 104. Shaft 104 further comprises a coiled,twisted or bent region 368. In the embodiment shown in FIG. 6H, coiled,twisted or bent region 368 is a spring attached to a proximal region ofshaft 104. A user can pass a suitable suture 362 around coiled, twistedor bent region 368 and secure substance delivery device 366 to ananatomical region. Suture 362 may be biodegradable or non-biodegradable.

One or more of the substance delivery devices disclosed herein maycomprise an elastic, super-elastic or shape-memory material. Such anelastic, super-elastic or shape-memory material may be used totemporarily reduce the profile of the substance delivery devices whilethey are being inserted or removed through the anatomy. For example,FIG. 7A shows a perspective view of an embodiment of a substancedelivery device comprising an elastic, super-elastic or shape-memorymaterial. Substance delivery device 370 of FIG. 7A comprises an elongateshaft 372. Shaft 372 has a sufficient strength to allow a user to pullsubstance delivery device 370 out of an anatomical region aftersubstance delivery device 370 has been placed in that anatomical region.Shaft 372 may be made of suitable biocompatible materials including, butnot limited to polymers such as polyethylene, Pebax, PEEK, etc.; metalsor metals alloys such as stainless steel, nickel-titanium alloys,titanium, etc. Substance delivery device 370 further comprises a loop374 located on the distal region of shaft 372. Loop 374 can be made fromsuitable elastic, super-elastic or shape-memory materials including, butnot limited to polymers; metals or metals alloys such as stainlesssteel, nickel-titanium alloys, titanium, etc. A region of loop 374 isattached to a distal region of shaft 372 as shown in FIG. 7A. During theinsertion of substance delivery device 370 into the anatomical region orremoval of substance delivery device 370 from the anatomical region,loop 374 may temporarily deform or bend to reduce the profile ofsubstance delivery device 370. After insertion of substance deliverydevice 370 into the anatomical region or removal of substance deliverydevice 370 from the anatomical region, loop 374 substantially regainsits original shape and orientation. Substance delivery device 370further comprises a cup shaped membrane 376. Membrane 376 may be coatedor impregnated with one or more substances to be delivered to thesurrounding anatomy. Membrane 376 is attached to substance deliverydevice 370 such that loop 374 is attached to the rim of the cup shapedmembrane 376. The concave surface of membrane 376 faces the proximaldirection and the convex surface of membrane 376 faces the distaldirection. Membrane 376 may be made of suitable biocompatible materialsincluding, but not limited to polyurethane, Nylon, polyethylene,silicon, etc. FIG. 7B shows a cross section through shaft 372 ofsubstance delivery device 370 of FIG. 7A through the plane 7B-7B.

FIG. 7C shows a perspective view of the substance delivery device ofFIG. 7A loaded on a delivery device. Delivery device 378 comprises adistal hollow tube 380. The inner diameter of distal hollow tube 380 islarger than the outer diameter of shaft 372. This allows a proximalregion of shaft 372 to be introduced into hollow tube 380 as shown inFIG. 7C. Delivery device 378 further comprises an elongate pusher 382attached to the proximal region of distal hollow tube 380. During amethod of deploying substance delivery device 370 into an anatomicalregion, a user pushes pusher 382 in the distal direction. This in turncauses the distal end of distal hollow tube 380 to push substancedelivery device 370 into the anatomical region. FIG. 7D shows a crosssection through the plane 7D-7D of FIG. 7C showing shaft 372 ofsubstance delivery device 370 of FIG. 7A enclosed by distal hollow tube380 of delivery device 378.

Substance delivery device 370 and delivery device 378 may be introducedinto the anatomy through one or more introducing devices. For example,FIG. 7E shows substance delivery device 370 of FIG. 7A loaded ondelivery device 378 of FIG. 7C being introduced through a guide catheter384. Guide catheter 384 comprises an elongate hollow introducing shaft386. The diameter of the lumen of introducing shaft 386 is larger thanthe outer diameter of delivery device 378. This allows a user tointroduce delivery device 378 through the lumen of introducing shaft386. Substance delivery device 370 may be present in a collapsed orfolded state within introducing shaft 386 and thereafter expand orunfold after being placed in a desired anatomical region. The proximalend of introducing shaft 386 may comprises a suitable hub such as afemale luer lock 388. Guide catheter 384 may in turn be introduced overa guidewire into an anatomical region. In the embodiment shown in FIG.7E, guide catheter 384 further comprises a rapid exchange lumen locatedon a short tube 390 attached to a distal region of introducing shaft386. The distal end of tube 390 and/or introducing shaft 386 maycomprise a radio-opaque marker 392 such as a radio-opaque marker band toenable the user to track guide catheter 384 using X-rays. The distal endof tube 390 and/or introducing shaft 386 may comprise an atraumatic tipto reduce or prevent damage to anatomical structures by the distal endof guide catheter 384.

One or more of the substance delivery devices disclosed herein maycomprise an elongate filament, coil or wire. Such substance deliverydevices may be introduced in an anatomical region through a suitableintroducing device. Such substance delivery devices may be fully orpartially biodegradable or non-biodegradable. Such substance deliverydevices may comprise an elastic, super-elastic or shape-memory materialto enable the substance delivery devices to assume a two or threedimensional shape after being deployed in an anatomical region. Forexample, FIG. 8A shows an embodiment of an elongate substance deliverydevice comprising an elongate filament being introduced in a sphenoidsinus. Substance delivery device 394 comprises an elongate filament canbe introduced into a suitable anatomical region such as a paranasalsinus to deliver one or more substances. The diameter of substancedelivery device 394 may range from 0.01 to 1 mm. This size allows mucousor other anatomical fluids to flow around substance delivery device 394and out of a paranasal sinus when substance delivery device 394 isinserted into the paranasal sinus. Substance delivery device 394 can bedelivered by a user into an anatomical region through a hollowintroducing device 396. In the embodiment shown in FIG. 8A, introducingdevice 396 comprises a hollow, elongate shaft 398 and a suitable hub 400connected to the proximal end of elongate shaft 398. FIG. 8B shows across sectional view through a region of substance delivery device 394of FIG. 8A through plane 8B-8B. In the embodiment shown, substancedelivery device 394 comprises an inner filament 402. Filament 402 may bemade of suitable biocompatible materials such as various biodegradableor non-biodegradable suture materials. Examples of such materialsinclude, but are not limited to poly-glycolic acid poly-L-lactic acid,polydioxanone, polyglyconate, Nylon, polyester, polypropylene, etc.Filament 402 may be manufactured by extrusion or drawing. Filament 402is coated with a basecoat. The basecoat in turn is dip coated or spraycoated with a matrix layer 404 comprising a substance to be delivered tothe surrounding anatomy. Matrix layer 404 in turn may be coated with atopcoat 406 to control diffusion and release rate of the substance inmatrix layer 404. In one embodiment, topcoat 406 is made of PBMA orphosphatidylcholine and the substance in matrix layer 404 is a steroid,antibiotic or an anti-fungal agent. In this embodiment, substancedelivery device 394 is delivered through an opening of a paranasal sinussuch that at least one region of substance delivery device 394 touches aregion of the mucosa of the paranasal sinus.

Several anatomical regions are lined by a layer of mucous that flows ina particular flow path. The devices and methods described herein may beused to selectively deliver a substance to an upstream region on themucous flow path. This upstream region may be chosen such that themucous flow delivers the substance throughout the anatomical region. Forexample, FIG. 9A shows a method of delivering a substance to the lateralwall of a maxillary sinus by the substance delivery device 296 of FIG.5B. Wick 300 of substance delivery device 296 touches the mucous layeron the lateral wall of the maxillary sinus. Thereafter, the substance ininflatable balloon 106 is delivered by wick 300 to the mucous on thelateral wall of the maxillary sinus at a controlled rate. The substanceis then transported along with the mucous flow to cover the entire innerwall of the maxillary sinus as shown in FIG. 9A.

In another example, FIG. 9B shows a method of delivering a substance tothe medial wall of a frontal sinus by a device similar to the substancedelivery device of FIG. 4L. Substance delivery device 408 of FIG. 9B issimilar to substance delivery device 240 of FIG. 4L. Substance deliverydevice 408 comprises an inflatable balloon 242 that acts as a substancereservoir. Inflatable balloon 242 further comprises one or more pores248. One or more pores 248 are located only on one side of inflatableballoon 242. One or more pores 248 are oriented so that they deliver thesubstance stored in inflatable balloon 242 at a controlled rate to themucous layer on the medial wall of a frontal sinus as shown in FIG. 9B.The substance is then transported along with the mucous flow to coverthe entire inner wall of the frontal sinus as shown in FIG. 9B.Substance delivery device 408 further comprises an orientation marker toensure that one or more pores 248 face the medial wall of the frontalsinus. In the embodiment shown in FIG. 9B, the orientation markercomprises a radiopaque marker 409 located on elongate shaft 104.Radiopaque marker 409 and one or more pores 248 are located in the sameradial direction from the axis of elongate shaft 104. This enables auser to orient one or more pores 248 to face the medial wall of thefrontal sinus under radiographic visualization.

One or more of the elongate devices disclosed herein may be used asstents. The stents may be positioned within natural or man-made openingsto the frontal, maxillary, sphenoid, anterior or posterior Ethmoidsinuses; other cells or cavities; anatomical regions such as nostrils,nasal cavities, nasal meatus, etc.; and other passageways such asEustachian tubes, naso-lachrymal ducts, etc.

For example, one or more of the elongate devices disclosed herein may beused as sinus stents. Sinus stents are used to prevent adhesions betweenmucosal surfaces that have been cut during surgical procedures such asFESS. Current sinus stents are bulky. They are difficult to insert andremove. Also, they are difficult to insert through small openings.Therefore low profile stents are needed to minimize invasiveness duringinsertion, removal and during the period they are implanted. One or moreof the elongate devices disclosed herein including, but not limited tothe devices illustrated in FIGS. 1, 2A, 4E, 4E′ and 4M may be used assinus stents. Such sinus stents may comprise one or more anchors orother mechanisms to secure the position of the sinus stents in theanatomy. Such sinus stents may for example be placed in anterior orposterior Ethmoid ostia or artificial openings leading to Ethmoidsinuses, natural or surgically created openings to other paranasalsinuses, etc. The step of placement of such sinus stents may be precededby a step of surgically modifying an anatomical region. For example, auser may surgically create an artificial opening to the Ethmoid sinusesand thereafter place a sinus stent through the artificial opening.

FIGS. 10A through 10C show the various steps of a method of implanting asubstance delivering stent in an anatomical region. The stent may bebiodegradable or non-biodegradable. In one embodiment of a biodegradablestent, the stent is made of a combination of PLLA and PGA. In anotherembodiment of a biodegradable stent, the stent is made of a combinationof mometasone furoate and poly(ester urethane) multi-block copolymers.The poly(ester urethane) multi-block copolymers may be made by combiningdifferent combinations of DL-lactide, glycolide, ε-caprolactone andpolyethylene glycol. The stent may be made of a rolled sheet of amaterial or a tube. In the example shown in FIG. 10A, stent 410comprises a rolled sheet of a biocompatible material. The rolled sheetcomprises one or more substances to be delivered to an anatomical regionwhere stent 410 is delivered. Stent 410 may comprise one or more windowsor slots 412 that allow a fluid to pass through the wall of stent 410.Such a stent 410 does not substantially disrupt the normal drainage ofanatomical fluids in the anatomical region. Stent 410 may be used todeliver steroids or other substances to anatomical regions including,but not limited to sinus ostia and/or passageways over a desired periodof time. In one embodiment, stent 410 is a self-expanding stent. Such asself-expanding stent 410 may be introduced through a hollow guide orsheath into an anatomical region. Stent 410 may be pushed out of thehollow sheath or guide by a pusher. In the method embodiment shown inFIGS. 10A through 10C, stent 410 is a balloon-expandable stent insertedin an anatomical region by a balloon catheter 414. Balloon catheter 414comprises an elongate shaft 416 and an inflatable balloon 418 on thedistal end of elongate shaft 416. Inflatable balloon 418 may be made ofsuitable compliant, non-compliant or semi-compliant materials. Stent 410is tightly rolled on the surface of inflatable balloon 418. This reducesthe profile of stent 410. Balloon catheter 414 and stent 410 areinserted into an anatomical region. In FIG. 10A, an ostium of aparanasal sinus is used as an example of the anatomical region. In FIG.10B, inflatable balloon 418 is inflated by a user. This causes stent 410to expand as shown in FIG. 10B. In one embodiment, inflatable balloon418 is also used as a dilating balloon to dilate the anatomical region.Thereafter, inflatable balloon 418 is deflated. This causes stent 410 toseparate from balloon catheter 414. Thereafter, as shown in FIG. 10C,balloon catheter 414 is removed from the anatomical region. Stent 410remains in the anatomical region. Stent 410 encloses a hollow regionthat allows a user to pass a range of devices through the hollow region.Examples of such devices include, but are not limited to guidewires,catheters, flexible scopes and cutters.

In one embodiment, the material of stent 410 comprises a polymer, one ormore substances to be delivered and a stabilizer. Stent 410 may bedesigned to delivery a substance through only one surface of the rolledsheet. FIG. 10D shows a cross section through a region 10D of anembodiment of the device of FIG. 10C. In the embodiment of stent 410shown in FIG. 10D, the wall of stent 410 comprises three layers. Innerlayer 420 is thick and provides mechanical strength to stent 410. In oneexample, inner layer 420 is made of ethylene vinyl acetate (EVA). Middlelayer 422 comprises a suitable substance to be delivered to thesurrounding anatomy. In one example, middle layer 422 comprises amixture of EVA and dexamethasone and polyvinyl pyrrolidone. Thesubstance to be delivered to the surrounding anatomy cannot diffusethrough inner layer 420, but can diffuse through an outer layer 424.Outer layer 424 thus controls the rate of release of the substance tothe surrounding anatomy. In one example, outer layer is made of EVA.Stent 410 is designed to be easily removable after a desired period oftime. Stent 410 may be removed for example by forceps or other graspingdevices. In one embodiment, stent 410 comprises a removal element thatenables a user to easily remove stent 410 from the anatomy. In oneembodiment, the removal element of an elongate string or filamentattached to stent 410. A user pulls the elongate string or filament inthe proximal direction to remove stent 410 from the anatomical region.

The various substance delivery devices disclosed herein may comprise ahollow tubular region through which anatomical fluids can flow. Suchembodiments of substance delivery devices cause minimal or zerodisruption to the natural flow of anatomical fluids such as mucous. Suchembodiments of substance delivery devices may also be used to preventadhesions between mucosal surfaces that have been cut during surgicalprocedures such as FESS. For example, FIGS. 11A through 11C show asequence of steps to deliver a substance delivery device through a sinusostium that prevents post-surgical adhesions and also allows the naturalflow of mucous through the sinus ostium. FIG. 11A shows a cross sectionof a sinus ostium OS of a patient with sinusitis. In FIG. 11B, the sinusostium OS is surgically dilated. This dilation may be performed by avariety of methods including, but not limited to the Balloon Sinuplasty™procedure, FESS, etc. Thereafter, in FIG. 11C, a substance deliverydevice 428 is inserted through the sinus ostium OS. Substance deliverydevice 428 comprises an elongate shaft 104 and a substance reservoir106. The outer diameter D.sub.1 of elongate shaft 104 is slightlysmaller than the inner diameter D.sub.2 of the dilated sinus ostium OS.This enables a user to introduce substance delivery device 248 throughthe dilated sinus ostium OS. Elongate shaft comprise an end-to-endlumen. This end-to-end lumen allows the natural flow of mucous generatedwithin the sinus thereby preventing unwanted accumulation of the mucouswithin the sinus. Elongate shaft 104 also prevents prevent adhesionsbetween mucosal surfaces of the sinus ostium OS that have been dilatedthereby acting as a sinus stent.

The stent devices disclosed herein may be retained in the anatomy for adesired time period ranging from approximately 3 days to approximately 4weeks. Such stents may be implanted in suitable anatomical regions suchas surgically enlarged or dilated opening(s) of a paranasal sinus. Theymay be sized to maintain a desired diameter of said surgically enlargedor dilated opening between about 2 mm and about 10 mm.

The devices and methods disclosed herein may be used to deliversubstances to anatomical regions such as paranasal sinuses by drippingand evaporation of the substances. In one method embodiment,dexamethasone is delivered to paranasal sinuses. In this embodiment,dexamethasone is dissolved in a volatile solvent such as ethanol toachieve a solution with a desired dexamethasone concentration (e.g. 10mg/ml). A substance delivery device such as substance delivery device240 of FIG. 4L is then inserted into a paranasal sinus. A suitablevolume of the solution (e.g. approx. 0.2 ml) is then delivered toinflatable balloon 242 of drug delivery device 240. The solution is thenallowed to drip and evaporate slowly through one or more pores 248located on inflatable balloon 242. The size of one or more pores 248 mayrange from 20 to 100 microns. Dripping and evaporation of the solutionthrough one or more pores 248 of substance delivery device 240 causesthe dexamethasone to be delivered to the inner walls of the paranasalsinuses. Similarly, other devices disclosed herein such as substancedelivery device 296 of FIG. 5B may be used to deliver substances toanatomical regions such as paranasal sinuses by dripping and evaporationof the substances.

The devices and methods disclosed herein may be used to deliver gels orviscous liquids comprising one or more substances to anatomical regionssuch as paranasal sinuses. Such gels or viscous liquids may coat andadhere to a mucous membrane and thus provide sustained delivery of oneor more substances to the mucous membrane. In one embodiment, aplasticized hydrocarbon gel comprising gelatin, pectin and sodiumcarboxymethylcellulose and a suitable substance may be delivered to amucous membrane such as the mucous membrane of a paranasal sinus. Suchgels can be used for sustained delivery of the suitable substance to themucous membrane.

One or more of the substance reservoirs disclosed herein may comprisemultiple compartments such that each compartment stores a particularsubstance formulation. The multiple compartments prevent mixing ofmultiple substance formulations before substance formulations aredelivered to the anatomy.

One or more of the substance reservoirs comprising pores may be filledwith a suitable substance at a sufficiently high pressure to cause aportion of the substance to squirt out of the pores. This process may beused to deliver an initial bolus of the substance to the surroundinganatomy.

One or more of the substance reservoirs disclosed herein may be filledwith a suitable substance after the substance reservoir is introduced inan anatomical region. Alternatively, one or more of the substancereservoirs disclosed herein may be filled with a suitable substancebefore the substance reservoir is introduced in an anatomical region.Alternatively, one or more of the substance reservoirs disclosed hereinmay be pre-filled with a solid, lyophilized or concentrated substance.The solid, lyophilized or concentrated substance is converted to anactive form by introducing a solvent into the substance reservoir. Thismay be done just before or after the substance reservoir is introducedin an anatomical region. Alternatively, one or more of the substancereservoirs disclosed herein may be pre-filled with an inactive form of asubstance. The inactive form of the substance is converted to an activeform by introducing an activating agent into the substance reservoir.This may be done just before or after the substance reservoir isintroduced in an anatomical region.

The devices and methods disclosed herein may be used to treat middle earor inner ear pathologies. This may be done by accessing the middle earthrough the Eustachian tube or through the tympanum. For example, thedevices and methods disclosed herein may be used to treat Meniere'sdisease by delivering gentamicin to the inner ear through the roundwindow membrane. The devices and methods disclosed herein may be used totreat a variety of diseases or disorders by a variety of substancesincluding, but not limited to the substances and diseases or disordersdisclosed in Table 1.

TABLE 1 ANATOMICAL LOCATION OF DISEASE/ EXAMPLES OF THE DISEASE/DISORDER SUBSTANCES THAT MAY DISORDER TO BE TREATED BE DELIVERED Innerear Meniere's disease, Gentamicin, Vestibular Vertigo suppressants (e.g.anticholinergics, antihistamines, and benzodiazepines), antiemeticdrugs, diuretics, etc. Inner ear Autoimmune inner Corticosteroids, etc.ear disease Inner ear Free radical induced Glutamate antagonists(e.g.damage memantine, caroverine and magnesium), Calpain inhibitor (e.g.Leupeptin), Antioxidants (e.g. glutathione, Methionine), etc. Inner earHearing loss and Neurotrophic factors (e.g. tinnitus NeuroTrophin-3),Genes for Neurotrophic factors such as BDNF (brain-derived neurotropicfactor), etc. Middle ear Otitis media Amoxicillin, ampicillin,azithromycin, cefaclor, cefdinir, ceftibuten, ceftriaxone, erythomycin,clarithromycin, combination of trimethoprim/sulfamethoxazole, ofloxacin,etc. Inner ear Degeneration of Grafted neural stem cells, inner earcells, embryonic stem cells, dorsal especially sensory ganglion cellsand cell lines hair cells and derived from fetal inner ear associatedneurons, cells, autologous bone marrow stromal cells, etc.

It is to be further appreciated that, as described herein, theimplantable portion of a substance delivery device 100 may include athrough lumen that may function as a vent and/or drain when suchimplantable portion device is in the Eustachian tube or through anopening formed in the tympanum.

The devices and methods disclosed herein may be used to mark ananatomical region with a suitable imageable marker. For example, thedevices and methods disclosed herein may be used to deliver a radioopaque marker such as a radio opaque contrast agent to an ostium of aparanasal sinus. This enables a user to image the ostium of theparanasal sinus using X-rays or fluoroscopy.

One or more of the substance delivery devices disclosed herein maycomprise a curved, bent or angled region to enable the drug deliverydevices to navigate through the anatomy.

The distal-most regions of one or more substance delivery devicesdisclosed herein may comprise an atraumatic tip. The atraumatic tip isused to prevent or reduce damage to the anatomy by the distal-mostregions of the one or more substance delivery devices.

The outer surface of one of more substance delivery devices disclosedherein may comprise a coating that reduces or eliminates the risk ofencrusting of the outer surface by a biological material. In oneembodiment, the coating comprises a material that absorbs water to forma gel. Examples of such materials include, but are not limited tohyaluronic acid, etc.

One or more of the substance delivery devices disclosed herein may bedesigned to be easily removable from the anatomy after completion of atreatment.

One or more of the substance delivery devices disclosed herein may berefilled after a significant volume of substance filled in a substancereservoir has been delivered to the anatomy.

One or more of the substance delivery devices disclosed herein maycomprise one or more markers to enable a user to locate and/or navigatethe substance delivery devices through the anatomy. For example, thesubstance delivery devices may comprise visual markers to enable theuser to determine the depth of insertion of the substance deliverydevices into the anatomy. In another example, the substance deliverydevices may comprise imaging markers to enable the user to locate and/ornavigate the substance delivery devices using imaging modalities such asX-rays, MRI, etc.

As used herein, the term “opening or a paranasal sinus” shall includeany transnasally accessible opening in a paranasal sinus or air cellsuch as natural ostia, surgically altered natural ostia, surgicallycreated openings, antrostomy openings, ostiotomy openings, burr holes,drilled holes, ethmoidectomy openings, natural or man made passageways,etc.

As used herein, the term “implantable” shall include any device that ismaintained in the body of a human or animal for a period ranging from 30minutes to 60 days.

As used herein, the term “porous” shall include any element thatcomprises one or more pores or apertures.

It is to be appreciated that the invention has been described hereabovewith reference to certain examples or embodiments of the invention butthat various additions, deletions, alterations and modifications may bemade to those examples and embodiments without departing from theintended spirit and scope of the invention. For example, any element orattribute of one embodiment or example may be incorporated into or usedwith another embodiment or example, unless to do so would render theembodiment or example unsuitable for its intended use. All reasonableadditions, deletions, modifications and alterations are to be consideredequivalents of the described examples and embodiments and are to beincluded within the scope of the following claims.

1. A method for delivering a substance into a paranasal sinus of asubject, the method comprising: advancing an expandable reservoir, in anunexpanded configuration, into a paranasal sinus of the subject, thereservoir being coupled with a reservoir filling tube having a lumenthrough which the substance is introduced into the reservoir, thereservoir having a barrier that controls the rate at which the substancepasses out of the reservoir; introducing a substance through the lumenof the reservoir filling tube and into the reservoir, thereby causingthe reservoir to fill and expand; detaching the reservoir filling tubefrom the reservoir; and removing the reservoir filling tube from thesubject, thus leaving the reservoir behind such that the substance willpass out of the reservoir through the barrier of the expandablereservoir at a predetermined rate.
 2. The method of claim 1, wherein theparanasal sinus includes an ostium of the paranasal sinus.
 3. The methodof claim 1, wherein the substance is a therapeutic substance.
 4. Themethod of claim 3, wherein the therapeutic substance comprises a drug.5. The method of claim 4, wherein the barrier is adapted to release thedrug from the reservoir over an extended period of time.
 6. The methodof claim 5, wherein the extended period of time ranges from about 30minutes to about 60 days.
 7. The method of claim 1, wherein thesubstance is a diagnostic substance.
 8. The method of claim 1, whereinthe reservoir, when filled, has a size and shape adapted to engage aparanasal sinus wall in a manner that limits movement of the reservoir.9. The method of claim 8, wherein the reservoir, when filled, is toolarge to pass through an opening of the paranasal sinus.
 10. The methodof claim 1, further comprising preventing the substance from backflowingout of the reservoir after removal of the tube.
 11. The method of claim10, wherein the reservoir comprises a reservoir lumen in fluidcommunication with the lumen of the tube, and wherein preventing thesubstance from backflowing out of the reservoir comprises preventing thesubstance from flowing out of the reservoir lumen.
 12. The method ofclaim 11, wherein the step of preventing backflow comprises a closuremechanism in the reservoir lumen closing.
 13. The method of claim 13,wherein the closure mechanism comprises a one-way valve.
 14. The methodof claim 1, further comprising viewing a marker on the tube duringadvancement of the reservoir to approximate a location of the reservoirrelative to the paranasal sinus.
 15. The method of claim 1, furthercomprising anchoring the reservoir to tissue of the subject.
 16. Themethod of claim 1, wherein the barrier comprises an expandable outerwall of the reservoir having multiple apertures, and wherein thesubstance passes out of at least some of the apertures at thepredetermined rate.
 17. The method of claim 1, wherein the reservoir isat least partially biodegradable.
 18. The method of claim 1, wherein thesubstance is selected from the group consisting of: an imageablecontrast agent; a diagnostic indicator agent; an antibiotic; anantifungal; an antiparasitic; an antimicrobial; a steroid; avasoconstrictor; a leukotriene inhibitor; an IgE inhibitor; ananti-inflammatory; a mast cell stabilizer; an antihistamine; animmunomodulator; a chemotherapeutic agent; an antineoplastic agent; amucolytic agent; an agent that thins or otherwise changes the viscosityof mucus; and a substance that facilitates remodeling of soft tissueand/or bone and/or cartilage.
 19. The method of claim 1, wherein thereservoir comprises a tubular member forming a reservoir lumen and aone-way valve in the lumen, wherein introducing the substance comprisesintroducing it through the reservoir lumen and the one-way valve intothe reservoir.
 20. The method of claim 1, wherein the reservoir fillingtube further comprises a guidewire lumen, and wherein the method furthercomprises: inserting a guidewire into the paranasal sinus beforeadvancing the reservoir; and advancing the reservoir filling tube overthe guidewire to advance the reservoir into the paranasal sinus.
 21. Themethod of claim 20, wherein the guidewire lumen extends from a distalopening in a distal end of the reservoir to a proximal opening in aproximal end of the reservoir filling tube.
 22. The method of claim 20,wherein the guidewire lumen extends from a distal opening in a distalend of the reservoir to a side opening located between proximal anddistal ends of the reservoir filling tube.
 23. The method of claim 1,wherein detaching the reservoir filling tube from the reservoircomprises cutting the filling tube.